Abstract
Neuro–immune interactions are widely manifested in animal physiology. Since immunity competes for energy with other physiological functions, it is subject to a circadian trade-off between other energy-demanding processes, such as neural activity, locomotion and thermoregulation. When immunity is challenged, this trade-off is tilted to an adaptive energy protecting and reallocation strategy that is identified as ‘sickness behaviour’. We review diverse disease-avoidant behaviours in the context of ingestion, indicating that several adaptive advantages have been acquired by animals (including humans) during phylogenetic evolution and by ontogenetic experiences: (i) preventing waste of energy by reducing appetite and consequently foraging/hunting (illness anorexia), (ii) avoiding unnecessary danger by promoting safe environments (preventing disease encounter by olfactory cues and illness potentiation neophobia), (iii) help fighting against pathogenic threats (hyperthermia/somnolence), and (iv) by associative learning evading specific foods or environments signalling danger (conditioned taste avoidance/aversion) and/or at the same time preparing the body to counteract by anticipatory immune responses (conditioning immunomodulation). The neurobiology behind disease-avoidant ingestive behaviours is reviewed with special emphasis on the body energy balance (intake versus expenditure) and an evolutionary psychology perspective.
Footnotes
References
- 1
Ader R., Cohen N.& Felten D. . 1995Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet 345, 99–103.doi:10.1016/S0140-6736(95)90066-7 (doi:10.1016/S0140-6736(95)90066-7). Crossref, PubMed, ISI, Google Scholar - 2
Salzet M. . 2000Invertebrate molecular neuroimmune processes. Brain Res. Brain Res. Rev. 34, 69–79.doi:10.1016/S0165-0173(00)00041-2 (doi:10.1016/S0165-0173(00)00041-2). Crossref, PubMed, Google Scholar - 3
Ottaviani E.& Franceschi C. . 1996The neuroimmunology of stress from invertebrates to man. Prog. Neurobiol. 48, 421–440.doi:10.1016/0301-0082(95)00049-6 (doi:10.1016/0301-0082(95)00049-6). Crossref, PubMed, ISI, Google Scholar - 4
Farr M., Zhu D. F., Povelones M., Valcich D.& Ambron R. T. . 2001Direct interactions between immunocytes and neurons after axotomy in aplysia. J. Neurobiol. 46, 89–96.doi:10.1002/1097-4695(20010205)46:2<89::AID-NEU20>3.0.CO;2-D (doi:10.1002/1097-4695(20010205)46:2<89::AID-NEU20>3.0.CO;2-D). Crossref, PubMed, Google Scholar - 5
Mallon E. B., Brockmann A.& Schmid-Hempel P. . 2003Immune response inhibits associative learning in insects. Proc. R. Soc. Lond. B 270, 2471–2473.doi:10.1098/rspb.2003.2456 (doi:10.1098/rspb.2003.2456). Link, ISI, Google Scholar - 6
Riddell C. E.& Mallon E. B. . 2006Insect psychoneuroimmunology: immune response reduces learning in protein starved bumblebees (Bombus terrestris). Brain Behav. Immun. 20, 135–138.doi:10.1016/j.bbi.2005.06.008 (doi:10.1016/j.bbi.2005.06.008). Crossref, PubMed, ISI, Google Scholar - 7
Schedlowski M. . 2006Insecta immune–cognitive interactions. Brain Behav. Immun. 20, 133–134.doi:10.1016/j.bbi.2005.09.004 (doi:10.1016/j.bbi.2005.09.004). Crossref, PubMed, ISI, Google Scholar - 8
Sadd B. M.& Schmid-Hempel P. . 2008Principles of ecological immunology. Evol. Appl. 2, 113–121.doi:10.1111/j.1752-4571.2008.00057.x (doi:10.1111/j.1752-4571.2008.00057.x). Crossref, PubMed, ISI, Google Scholar - 9
Demas G. E. . 2004The energetics of immunity: a neuroendocrine link between energy balance and immune function. Horm. Behav. 45, 173–180.doi:10.1016/j.yhbeh.2003.11.002 (doi:10.1016/j.yhbeh.2003.11.002). Crossref, PubMed, ISI, Google Scholar - 10
Straub R. H., Cutolo M., Buttgereit F.& Pongratz G. . 2010Energy regulation and neuroendocrine–immune control in chronic inflammatory diseases. J. Intern. Med. 267, 543–560.doi:10.1111/j.1365-2796.2010.02218.x (doi:10.1111/j.1365-2796.2010.02218.x). Crossref, PubMed, ISI, Google Scholar - 11
Lochmiller R. L.& Deerenberg C. . 2000Trade-offs in evolutionary immunology. Oikos 88, 87–98.doi:10.1034/j.1600-0706.2000.880110.x (doi:10.1034/j.1600-0706.2000.880110.x). Crossref, ISI, Google Scholar - 12
Dantzer R., O'Connor J. C., Freund G. G., Johnson R. W.& Kelley K. W. . 2008From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9, 46–56.doi:10.1038/nrn2297 (doi:10.1038/nrn2297). Crossref, PubMed, ISI, Google Scholar - 13
Schedlowski M.& Pacheco-Lopez G. . 2010The learned immune response: Pavlov and beyond. Brain Behav. Immun. 24, 176–185.doi:10.1016/j.bbi.2009.08.007 (doi:10.1016/j.bbi.2009.08.007). Crossref, PubMed, ISI, Google Scholar - 14
Schaller M.& Park J. H. . 2011The behavioral immune system (and why it matters). Curr. Dir. Psychol. Sci. 20, 99–103.doi:10.1177/0963721411402596 (doi:10.1177/0963721411402596). Crossref, ISI, Google Scholar - 15
Schaller M.& Duncan L. A. . 2007The behavioral immune system: its evolution and social psychological implication. Evolution and the social mind: evolutionary psychology and social cognition (eds, Forgas J. P., Haselton M. G.& von Hippel W. ), pp. 293–307. New York, NY: Psychology Press. Google Scholar - 16
Neuberg S. L., Kenrick D. T.& Schaller M. . 2011Human threat management systems: self-protection and disease avoidance. Neurosci. Biobehav. Rev. 35, 1042–1051.doi:10.1016/j.neubiorev.2010.08.011 (doi:10.1016/j.neubiorev.2010.08.011). Crossref, PubMed, ISI, Google Scholar - 17
Oaten M., Stevenson R. J.& Case T. I. . 2009Disgust as a disease-avoidance mechanism. Psychol. Bull. 135, 303–321.doi:10.1037/a0014823 (doi:10.1037/a0014823). Crossref, PubMed, ISI, Google Scholar - 18
Tybur J. M., Merriman L. A., Hooper A. E. C., McDonald M. M.& Navarrete C. D. . 2010Extending the behavioral immune system to political psychology: are political conservatism and disgust sensitivity really related?Evol. Psychol-Us. 8, 599–616. PubMed, ISI, Google Scholar - 19
Bloom D. . 2004Is acne really a disease? A theory of acne as an evolutionarily significant, high-order psychoneuroimmune interaction timed to cortical development with a crucial role in mate choice. Med. Hypotheses 62, 462–469.doi:10.1016/j.mehy.2003.11.003 (doi:10.1016/j.mehy.2003.11.003). Crossref, PubMed, ISI, Google Scholar - 20
Ader R., Cohen N.& Bovbjerg D. . 1982Conditioned suppression of humoral immunity in the rat. J. Comp. Physiol. Psychol. 96, 517–521.doi:10.1037/h0077887 (doi:10.1037/h0077887). Crossref, PubMed, ISI, Google Scholar - 21
Alvarez-Borda B., Ramirez-Amaya V., Perez-Montfort R.& Bermudez-Rattoni F. . 1995Enhancement of antibody production by a learning paradigm. Neurobiol. Learn Mem. 64, 103–105.doi:10.1006/nlme.1995.1048 (doi:10.1006/nlme.1995.1048). Crossref, PubMed, ISI, Google Scholar - 22
Goebel M. U., 2002Behavioral conditioning of immunosuppression is possible in humans. FASEB J. 16, 1869–1873.doi:10.1096/fj.02-0389com (doi:10.1096/fj.02-0389com). Crossref, PubMed, ISI, Google Scholar - 23
Bermudez-Rattoni F. . 2010Is memory consolidation a multiple-circuit system?Proc. Natl Acad. Sci. USA 107, 8051–8052.doi:10.1073/pnas.1003434107 (doi:10.1073/pnas.1003434107). Crossref, PubMed, ISI, Google Scholar - 24
Goehler L. E., Gaykema R. P., Hansen M. K., Anderson K., Maier S. F.& Watkins L. R. . 2000Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton. Neurosci. 85, 49–59.doi:10.1016/S1566-0702(00)00219-8 (doi:10.1016/S1566-0702(00)00219-8). Crossref, PubMed, ISI, Google Scholar - 25
Blalock J. E. . 2005The immune system as the sixth sense. J. Intern. Med. 257, 126–138.doi:10.1111/j.1365-2796.2004.01441.x (doi:10.1111/j.1365-2796.2004.01441.x). Crossref, PubMed, ISI, Google Scholar - 26
Quan N.& Banks W. A. . 2007Brain-immune communication pathways. Brain Behav. Immun. 21, 727–735.doi:10.1016/j.bbi.2007.05.005 (doi:10.1016/j.bbi.2007.05.005). Crossref, PubMed, ISI, Google Scholar - 27
Haas H. S.& Schauenstein K. . 1997Neuroimmunomodulation via limbic structures—the neuroanatomy of psychoimmunology. Prog. Neurobiol. 51, 195–222.doi:10.1016/S0301-0082(96)00055-X (doi:10.1016/S0301-0082(96)00055-X). Crossref, PubMed, ISI, Google Scholar - 28
Gautron L.& Laye S. . 2009Neurobiology of inflammation-associated anorexia. Front. Neurosci. 3, 59. PubMed, ISI, Google Scholar - 29
Maier S. F.& Watkins L. R. . 2000The immune system as a sensory system: implications for psychology. Curr. Dir. Psychol. Sci. 9, 98–102.doi:10.1111/1467-8721.00069 (doi:10.1111/1467-8721.00069). Crossref, ISI, Google Scholar - 30
Berthoud H. R.& Neuhuber W. L. . 2000Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 85, 1–17.doi:10.1016/S1566-0702(00)00215-0 (doi:10.1016/S1566-0702(00)00215-0). Crossref, PubMed, ISI, Google Scholar - 31
Guijarro A., Laviano A.& Meguid M. M. . 2006Hypothalamic integration of immune function and metabolism. Prog. Brain Res. 153, 367–405.doi:10.1016/S0079-6123(06)53022-5 (doi:10.1016/S0079-6123(06)53022-5). Crossref, PubMed, ISI, Google Scholar - 32
Harrison N. A., Brydon L., Walker C., Gray M. A., Steptoe A.& Critchley H. D. . 2009Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol. Psychiatr. 66, 407–414.doi:10.1016/j.biopsych.2009.03.015 (doi:10.1016/j.biopsych.2009.03.015). Crossref, PubMed, ISI, Google Scholar - 33
Harrison N. A., Brydon L., Walker C., Gray M. A., Steptoe A., Dolan R. J.& Critchley H. D. . 2009Neural origins of human sickness in interoceptive responses to inflammation. Biol. Psychiatr. 66, 415–422.doi:10.1016/j.biopsych.2009.03.007 (doi:10.1016/j.biopsych.2009.03.007). Crossref, PubMed, ISI, Google Scholar - 34
Harrison N. A., Gray M. A., Gianaros P. J.& Critchley H. D. . 2010The embodiment of emotional feelings in the brain. J. Neurosci. 30, 12 878–12 884.doi:10.1523/JNEUROSCI.1725-10.2010 (doi:10.1523/JNEUROSCI.1725-10.2010). Crossref, ISI, Google Scholar - 35
Doenlen R., Krugel U., Wirth T., Riether C., Engler A., Prager G., Engler H., Schedlowski M.& Pacheco-Lopez G. . 2011Electrical activity in rat cortico-limbic structures after single or repeated administration of lipopolysaccharide or staphylococcal enterotoxin B. Proc. R. Soc. B 278, 1864–1872.doi:10.1098/rspb.2010.2040 (doi:10.1098/rspb.2010.2040). Link, ISI, Google Scholar - 36
Pacheco-Lopez G., Niemi M. B., Kou W., Harting M., Fandrey J.& Schedlowski M. . 2005Neural substrates for behaviorally conditioned immunosuppression in the rat. J. Neurosci. 25, 2330–2337.doi:10.1523/JNEUROSCI.4230-04.2005 (doi:10.1523/JNEUROSCI.4230-04.2005). Crossref, PubMed, ISI, Google Scholar - 37
Riviere S., Challet L., Fluegge D., Spehr M.& Rodriguez I. . 2009Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors. Nature 459, 574–577.doi:10.1038/nature08029 (doi:10.1038/nature08029). Crossref, PubMed, ISI, Google Scholar - 38
Serrats J.& Sawchenko P. E. . 2009How T-cell-dependent and -independent challenges access the brain: vascular and neural responses to bacterial lipopolysaccharide and staphylococcal enterotoxin B. Brain Behav. Immun. 23, 1038–1052.doi:10.1016/j.bbi.2009.06.004 (doi:10.1016/j.bbi.2009.06.004). Crossref, PubMed, ISI, Google Scholar - 39
Banks W. A.& Erickson M. A. . 2010The blood-brain barrier and immune function and dysfunction. Neurobiol. Dis. 37, 26–32.doi:10.1016/j.nbd.2009.07.031 (doi:10.1016/j.nbd.2009.07.031). Crossref, PubMed, ISI, Google Scholar - 40
Ferrero D. M.& Liberles S. D. . 2010The secret codes of mammalian scents. Wiley Interdiscip. Rev. Syst. Biol. Med. 2, 23–33.doi:10.1002/wsbm.39 (doi:10.1002/wsbm.39). Crossref, PubMed, ISI, Google Scholar - 41
Migeotte I., Communi D.& Parmentier M. . 2006Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev. 17, 501–519.doi:10.1016/j.cytogfr.2006.09.009 (doi:10.1016/j.cytogfr.2006.09.009). Crossref, PubMed, ISI, Google Scholar - 42
Le Y., Murphy P. M.& Wang J. M. . 2002Formyl-peptide receptors revisited. Trends Immunol. 23, 541–548.doi:10.1016/S1471-4906(02)02316-5 (doi:10.1016/S1471-4906(02)02316-5). Crossref, PubMed, ISI, Google Scholar - 43
Le Y., Wang J. M., Liu X., Kong Y., Hou X., Ruan L.& Mou H. . 2007Biologically active peptides interacting with the G protein-coupled formylpeptide receptor. Protein Pept. Lett. 14, 846–853.doi:10.2174/092986607782110211 (doi:10.2174/092986607782110211). Crossref, PubMed, ISI, Google Scholar - 44
Bomback A. . 2006The physical exam and the sense of smell. N. Engl. J. Med. 354, 327–329.doi:10.1056/NEJMp048244 (doi:10.1056/NEJMp048244). Crossref, PubMed, ISI, Google Scholar - 45
Persaud K., Pisanelli A.& Bailey A. . 2009Woundmonitor (ECRO 2008 meeting). Chem. Senses 3, E37. Google Scholar - 46
Exton M. S. . 1997Infection-induced anorexia: active host defence strategy. Appetite 29, 369–383. Crossref, PubMed, ISI, Google Scholar - 47
Langhans W. . 2000Anorexia of infection: current prospects. Nutrition 16, 996–1005.doi:10.1016/S0899-9007(00)00421-4 (doi:10.1016/S0899-9007(00)00421-4). Crossref, PubMed, ISI, Google Scholar - 48
Nava F.& Carta G. . 2000Repeated lipopolysaccharide administration produces tolerance to anorexia and fever but not to inhibition of thirst in rat. Int. J. Immunopharmacol. 22, 943–953.doi:10.1016/S0192-0561(00)00058-8 (doi:10.1016/S0192-0561(00)00058-8). Crossref, PubMed, ISI, Google Scholar - 49
DellaGioia N.& Hannestad J. . 2010A critical review of human endotoxin administration as an experimental paradigm of depression. Neurosci. Biobehav. Rev. 34, 130–143.doi:10.1016/j.neubiorev.2009.07.014 (doi:10.1016/j.neubiorev.2009.07.014). Crossref, PubMed, ISI, Google Scholar - 50
Brebner K., Hayley S., Zacharko R., Merali Z.& Anisman H. . 2000Synergistic effects of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha: central monoamine, corticosterone, and behavioral variations. Neuropsychopharmacology 22, 566–580.doi:10.1016/S0893-133X(99)00166-9 (doi:10.1016/S0893-133X(99)00166-9). Crossref, PubMed, ISI, Google Scholar - 51
Yang Z. J., Koseki M., Meguid M. M., Gleason J. R.& Debonis D. . 1994Synergistic effect of rhTNF-alpha and rhIL-1 alpha in inducing anorexia in rats. Am. J. Physiol. 267, R1056–R1064. PubMed, Google Scholar - 52
Langhans W., Savoldelli D.& Weingarten S. . 1993Comparison of the feeding responses to bacterial lipopolysaccharide and interleukin-1 beta. Physiol. Behav. 53, 643–649.doi:10.1016/0031-9384(93)90168-F (doi:10.1016/0031-9384(93)90168-F). Crossref, PubMed, ISI, Google Scholar - 53
Reichenberg A., Yirmiya R., Schuld A., Kraus T., Haack M., Morag A.& Pollmacher T. . 2001Cytokine-associated emotional and cognitive disturbances in humans. Arch. Gen. Psychiatr. 58, 445–452.doi:10.1001/archpsyc.58.5.445 (doi:10.1001/archpsyc.58.5.445). Crossref, PubMed, Google Scholar - 54
Reichenberg A., Kraus T., Haack M., Schuld A., Pollmacher T.& Yirmiya R. . 2002Endotoxin-induced changes in food consumption in healthy volunteers are associated with TNF-alpha and IL-6 secretion. Psychoneuroendocrinology 27, 945–956.doi:10.1016/S0306-4530(01)00101-9 (doi:10.1016/S0306-4530(01)00101-9). Crossref, PubMed, ISI, Google Scholar - 55
Hart B. L. . 1988Biological basis of the behavior of sick animals. Neurosci. Biobehav. Rev. 12, 123–137.doi:10.1016/S0149-7634(88)80004-6 (doi:10.1016/S0149-7634(88)80004-6). Crossref, PubMed, ISI, Google Scholar - 56
Wing E. J.& Young J. B. . 1980Acute starvation protects mice against Listeria monocytogenes. Infect. Immun. 28, 771–776. Crossref, PubMed, ISI, Google Scholar - 57
Weinberg E. D. . 1984Iron withholding: a defense against infection and neoplasia. Physiol. Rev. 64, 65–102. Crossref, PubMed, ISI, Google Scholar - 58
Bernstein I. L.& Fenner D. P. . 1983Learned food aversions: heterogeneity of animal models of tumor-induced anorexia. Appetite 4, 79–86. Crossref, PubMed, ISI, Google Scholar - 59
Bernstein I. L., Treneer C. M., Goehler L. E.& Murowchick E. . 1985Tumor growth in rats: conditioned suppression of food intake and preference. Behav. Neurosci. 99, 818–830.doi:10.1037/0735-7044.99.5.818 (doi:10.1037/0735-7044.99.5.818). Crossref, PubMed, ISI, Google Scholar - 60
Plata-Salaman C. R. . 1998Cytokines and anorexia: a brief overview. Semin. Oncol. 25((Suppl. 1 1)), 64–72. PubMed, ISI, Google Scholar - 61
Meguid M. M., Yang Z. J., Gleason J. R.& Kubota A. . 1999Differential feeding patterns induced by tumor growth and by TPN. Nutrition 15, 555–562.doi:10.1016/S0899-9007(99)00085-4 (doi:10.1016/S0899-9007(99)00085-4). Crossref, PubMed, ISI, Google Scholar - 62
Varma M., Chai J. K., Meguid M. M.& Yang Z. J. . 2001Gender differences in tumor-induced anorectic feeding pattern in Fischer-344 rats. Physiol. Behav. 74, 29–35.doi:10.1016/S0031-9384(01)00569-8 (doi:10.1016/S0031-9384(01)00569-8). Crossref, PubMed, ISI, Google Scholar - 63
Seruga B., Zhang H., Bernstein L. J.& Tannock I. F. . 2008Cytokines and their relationship to the symptoms and outcome of cancer. Nat. Rev. Cancer 8, 887–899.doi:10.1038/nrc2507 (doi:10.1038/nrc2507). Crossref, PubMed, ISI, Google Scholar - 64
Laviano A., Inui A., Marks D. L., Meguid M. M., Pichard C., Rossi Fanelli F.& Seelaender M. . 2008Neural control of the anorexia-cachexia syndrome. Am. J. Physiol. Endocrinol. Metab. 295, E1000–E1008.doi:10.1152/ajpendo.90252.2008 (doi:10.1152/ajpendo.90252.2008). Crossref, PubMed, ISI, Google Scholar - 65
Molfino A., Laviano A.& Rossi Fanelli F. . 2010Contribution of anorexia to tissue wasting in cachexia. Curr. Opin. Support Palliat. Care 4, 249–253.doi:10.1097/SPC.0b013e32833e4aa5 (doi:10.1097/SPC.0b013e32833e4aa5). Crossref, PubMed, Google Scholar - 66
Lehner M. D.& Hartung T. . 2002Endotoxin tolerance-mechanisms and beneficial effects in bacterial infection. Rev. Physiol. Biochem. Pharmacol. 144, 95–141.doi:10.1007/BFb0116586 (doi:10.1007/BFb0116586). Crossref, PubMed, ISI, Google Scholar - 67
West M. A.& Heagy W. . 2002Endotoxin tolerance: a review. Crit. Care Med. 30((Suppl. 1)), S64–S73.doi:10.1097/00003246-200201001-00009 (doi:10.1097/00003246-200201001-00009). Crossref, ISI, Google Scholar - 68
Zeisberger E.& Roth J. . 1998Tolerance to pyrogens. Ann. NY Acad. Sci. 856, 116–131.doi:10.1111/j.1749-6632.1998.tb08320.x (doi:10.1111/j.1749-6632.1998.tb08320.x). Crossref, PubMed, ISI, Google Scholar - 69
Engeland C. G., Nielsen D. V., Kavaliers M.& Ossenkopp K. P. . 2001Locomotor activity changes following lipopolysaccharide treatment in mice: a multivariate assessment of behavioral tolerance. Physiol. Behav. 72, 481–491.doi:10.1016/S0031-9384(00)00436-4 (doi:10.1016/S0031-9384(00)00436-4). Crossref, PubMed, ISI, Google Scholar - 70
Lal H.& Brown R. M. . 1969Effects of bacterial endotoxin on operant behavior of the rat. Toxicol. Appl. Pharmacol. 14, 41–47.doi:10.1016/0041-008X(69)90162-8 (doi:10.1016/0041-008X(69)90162-8). Crossref, PubMed, ISI, Google Scholar - 71
Langhans W., Balkowski G.& Savoldelli D. . 1991Differential feeding responses to bacterial lipopolysaccharide and muramyl dipeptide. Am. J. Physiol. 261, R659–R664. PubMed, ISI, Google Scholar - 72
Pacheco-Lopez G., Niemi M. B., Engler H., Engler A., Riether C., Doenlen R., Espinosa E., Oberbeck R.& Schedlowski M. . 2008Weakened [corrected] taste-LPS association during endotoxin tolerance. Physiol. Behav. 93, 261–266.doi:10.1016/j.physbeh.2007.08.022 (doi:10.1016/j.physbeh.2007.08.022). Crossref, PubMed, ISI, Google Scholar - 73
Murray R. J. . 2005Recognition and management of Staphylococcus aureus toxin-mediated disease. Intern. Med. J. 35((Suppl. 2)), S106–S119.doi:10.1111/j.1444-0903.2005.00984.x (doi:10.1111/j.1444-0903.2005.00984.x). Crossref, PubMed, ISI, Google Scholar - 74
Bergdoll M. S. . 1988Monkey feeding test for staphylococcal enterotoxin. Meth. Enzymol. 165, 324–333.doi:10.1016/S0076-6879(88)65048-8 (doi:10.1016/S0076-6879(88)65048-8). Crossref, PubMed, ISI, Google Scholar - 75
Dellabona P., Peccoud J., Kappler J., Marrack P., Benoist C.& Mathis D. . 1990Superantigens interact with MHC class II molecules outside of the antigen groove. Cell 62, 1115–1121.doi:10.1016/0092-8674(90)90388-U (doi:10.1016/0092-8674(90)90388-U). Crossref, PubMed, ISI, Google Scholar - 76
Hong S. C., Waterbury G.& Janeway C. A. . 1996Different superantigens interact with distinct sites in the Vbeta domain of a single T cell receptor. J. Exp. Med. 183, 1437–1446.doi:10.1084/jem.183.4.1437 (doi:10.1084/jem.183.4.1437). Crossref, PubMed, ISI, Google Scholar - 77
Bette M., Schafer M. K., van Rooijen N., Weihe E.& Fleischer B. . 1993Distribution and kinetics of superantigen-induced cytokine gene expression in mouse spleen. J. Exp. Med. 178, 1531–1539.doi:10.1084/jem.178.5.1531 (doi:10.1084/jem.178.5.1531). Crossref, PubMed, ISI, Google Scholar - 78
Sundstedt A., Dohlsten M., Hedlund G., Hoiden I., Bjorklund M.& Kalland T. . 1994Superantigens anergize cytokine production but not cytotoxicity in vivo. Immunology 82, 117–125. PubMed, ISI, Google Scholar - 79
Serrats J.& Sawchenko P. E. . 2006CNS activational responses to staphylococcal enterotoxin B: T-lymphocyte-dependent immune challenge effects on stress-related circuitry. J. Comp. Neurol. 495, 236–254.doi:10.1002/cne.20872 (doi:10.1002/cne.20872). Crossref, PubMed, ISI, Google Scholar - 80
Kusnecov A. W.& Goldfarb Y. . 2005Neural and behavioral responses to systemic immunologic stimuli: a consideration of bacterial T cell superantigens. Curr. Pharm. Des. 11, 1039–1046.doi:10.2174/1381612053381602 (doi:10.2174/1381612053381602). Crossref, PubMed, ISI, Google Scholar - 81
Pacheco-Lopez G., Niemi M. B., Kou W., Harting M., Del Rey A., Besedovsky H. O.& Schedlowski M. . 2004Behavioural endocrine immune-conditioned response is induced by taste and superantigen pairing. Neuroscience 129, 555–562.doi:10.1016/j.neuroscience.2004.08.033 (doi:10.1016/j.neuroscience.2004.08.033). Crossref, PubMed, ISI, Google Scholar - 82
Kawashima N.& Kusnecov A. W. . 2002Effects of staphylococcal enterotoxin A on pituitary–adrenal activation and neophobic behavior in the C57BL/6 mouse. J. Neuroimmunol. 123, 41–49.doi:10.1016/S0165-5728(01)00486-6 (doi:10.1016/S0165-5728(01)00486-6). Crossref, PubMed, ISI, Google Scholar - 83
Kusnecov A. W., Liang R.& Shurin G. . 1999T-lymphocyte activation increases hypothalamic and amygdaloid expression of CRH mRNA and emotional reactivity to novelty. J. Neurosci. 19, 4533–4543. Crossref, PubMed, ISI, Google Scholar - 84
Rossi-George A., Urbach D., Colas D., Goldfarb Y.& Kusnecov A. W. . 2005Neuronal, endocrine, and anorexic responses to the T-cell superantigen staphylococcal enterotoxin A: dependence on tumor necrosis factor-alpha. J. Neurosci. 25, 5314–5322.doi:10.1523/JNEUROSCI.0687-05.2005 (doi:10.1523/JNEUROSCI.0687-05.2005). Crossref, PubMed, ISI, Google Scholar - 85
Urbach-Ross D.& Kusnecov A. W. . 2009Impact of superantigenic molecules on central nervous system function. Front. Biosci. 14, 4416–4426.doi:10.2741/3537 (doi:10.2741/3537). Crossref, ISI, Google Scholar - 86
Garcia J., Lasiter P. S., Bermudez-Rattoni F.& Deems D. A. . 1985A general theory of aversion learning. Ann. NY Acad. Sci. 443, 8–21.doi:10.1111/j.1749-6632.1985.tb27060.x (doi:10.1111/j.1749-6632.1985.tb27060.x). Crossref, PubMed, ISI, Google Scholar - 87
Pacheco-Lopez G., Niemi M. B., Engler H.& Schedlowski M. . 2007Neuro-immune associative learning. Neural plasticity and memory from genes to brain imaging.Boca Raton, FL: CRC Press. Google Scholar - 88
Rescorla R. . 1988Behavioral studies of Pavlovian conditioning. Annu. Rev. Neurosci. 11, 329–352.doi:10.1146/annurev.ne.11.030188.001553 (doi:10.1146/annurev.ne.11.030188.001553). Crossref, PubMed, ISI, Google Scholar - 89
Pacheco-Lopez G., Engler H., Niemi M. B.& Schedlowski M. . 2009Taste–immune associative learning. Conditioned taste aversion (eds, Reilly S.& Schachtman T. ), pp. 473–496. New York, NY: Oxford University Press. Google Scholar - 90
Mirotti L., Mucida D., de Sa-Rocha L. C., Costa-Pinto F. A.& Russo M. . 2010Food aversion: a critical balance between allergen-specific IgE levels and taste preference. Brain Behav. Immun. 24, 370–375.doi:10.1016/j.bbi.2009.12.006 (doi:10.1016/j.bbi.2009.12.006). Crossref, PubMed, ISI, Google Scholar - 91
Costa-Pinto F. A., Basso A. S., Britto L. R. G., Malucelli B. E.& Russo M. . 2005Avoidance behavior and neural correlates of allergen exposure in a murine model of asthma. Brain Behav. Immun. 19, 52–60.doi:10.1016/j.bbi.2004.02.005 (doi:10.1016/j.bbi.2004.02.005). Crossref, PubMed, ISI, Google Scholar - 92
Costa-Pinto F. A., Basso A. S., De Sa-Rocha L. C., Britto L. R., Russo M.& Palermo-Neto J. . 2006Neural correlates of IgE-mediated allergy. Ann. NY Acad. Sci. 1088, 116–131.doi:10.1196/annals.1366.028 (doi:10.1196/annals.1366.028). Crossref, PubMed, ISI, Google Scholar - 93
Pinto A., Yanai M., Sekizawa K., Aikawa T.& Sasaki H. . 1995Conditioned enhancement of cough response in awake guinea pigs. Int. Arch. Allergy Immunol. 108, 95–98.doi:10.1159/000237124 (doi:10.1159/000237124). Crossref, PubMed, ISI, Google Scholar - 94
Parker L. A. . 2006The role of nausea in taste avoidance learning in rats and shrews. Auton. Neurosci. 125, 34–41.doi:10.1016/j.autneu.2006.01.010 (doi:10.1016/j.autneu.2006.01.010). Crossref, PubMed, ISI, Google Scholar - 95
Russell M., Dark K. A., Cummins R. W., Ellman G., Callaway E.& Peeke H. V. . 1984Learned histamine release. Science 225, 733–734.doi:10.1126/science.6205449 (doi:10.1126/science.6205449). Crossref, PubMed, ISI, Google Scholar - 96
Irie M., Maeda M.& Nagata S. . 2001Can conditioned histamine release occur under urethane anesthesia in guinea pigs?Physiol. Behav. 72, 567–573.doi:10.1016/S0031-9384(00)00438-8 (doi:10.1016/S0031-9384(00)00438-8). Crossref, PubMed, ISI, Google Scholar - 97
MacQueen G., Marshall J., Perdue M., Siegel S.& Bienenstock J. . 1989Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease II. Science 243, 83–85.doi:10.1126/science.2911721 (doi:10.1126/science.2911721). Crossref, PubMed, ISI, Google Scholar - 98
Palermo-Neto J.& Guimarães R. . 2000Pavlovian conditioning of lung anaphylactic response in rats. Life Sci. 68, 611–623.doi:10.1016/S0024-3205(00)00966-8 (doi:10.1016/S0024-3205(00)00966-8). Crossref, PubMed, ISI, Google Scholar - 99
Madden K. S., Boehm G. W., Lee S. C., Grota L. J., Cohen N.& Ader R. . 2001One-trial conditioning of the antibody response to hen egg lysozyme in rats. J. Neuroimmunol. 113, 236–239.doi:10.1016/S0165-5728(00)00448-3 (doi:10.1016/S0165-5728(00)00448-3). Crossref, PubMed, ISI, Google Scholar - 100
Husband A. J., Lin W., Madsen G.& King M. G. . 1993A conditioning model for immunostimulation: Enhancement of the antibody responses to ovalbumin by behavioral conditioning in rats. Psychoimmunology (ed.& Husband A. J. ), pp. 139–148. Boca Raton, FL: CRC Press. Google Scholar - 101
Chen J., Lin W., Wang W., Shao F., Yang J., Wang B., Kuang F., Duan X.& Ju G. . 2004Enhancement of antibody production and expression of c-Fos in the insular cortex in response to a conditioned stimulus after a single-trial learning paradigm. Behav. Brain Res. 154, 557–565.doi:10.1016/j.bbr.2004.03.024 (doi:10.1016/j.bbr.2004.03.024). Crossref, PubMed, ISI, Google Scholar - 102
Gustavson C. R., Kelly D. J.& Sweeney M. . 1976Prey-lithium aversion. I. coyotes and wolves. Behav. Biol. 17, 61–72.doi:10.1016/S0091-6773(76)90272-8 (doi:10.1016/S0091-6773(76)90272-8). Crossref, PubMed, Google Scholar - 103
Quick D. L., Gustavson C. R.& Rusiniak K. W. . 1985Coyote control and taste aversion. Appetite 6, 253–264. Crossref, PubMed, ISI, Google Scholar - 104
Ellins S. R.& Catalano S. M. . 1980Field application of the conditioned taste aversion paradigm to the control of coyote predation on sheep and turkeys. Behav. Neural Biol. 29, 532–536.doi:10.1016/S0163-1047(80)92882-4 (doi:10.1016/S0163-1047(80)92882-4). Crossref, PubMed, Google Scholar - 105
Scalera G. . 2002Effects of conditioned food aversions on nutritional behavior in humans. Nutr. Neurosci. 5, 159–188.doi:10.1080/10284150290013059 (doi:10.1080/10284150290013059). Crossref, PubMed, ISI, Google Scholar - 106
Ader R. . 1974Letter: behaviorially conditioned immunosuppression. Psychosom. Med. 36, 183–184. Crossref, PubMed, ISI, Google Scholar - 107
Bermudez-Rattoni F. . 2004Molecular mechanisms of taste-recognition memory. Nat. Rev. Neurosci. 5, 209–217.doi:10.1038/nrn1344 (doi:10.1038/nrn1344). Crossref, PubMed, ISI, Google Scholar - 108
Kiefer S. W. . 1985Neural mediation of conditioned food aversions. Ann. NY Acad. Sci. 443, 100–109.doi:10.1111/j.1749-6632.1985.tb27066.x (doi:10.1111/j.1749-6632.1985.tb27066.x). Crossref, PubMed, ISI, Google Scholar - 109
Hopkins S. J.& Rothwell N. J. . 1995Cytokines and the nervous system. I. Expression and recognition. Trends Neurosci. 18, 83–88.doi:10.1016/0166-2236(95)93881-W (doi:10.1016/0166-2236(95)93881-W). Crossref, PubMed, ISI, Google Scholar - 110
Rothwell N. J.& Hopkins S. J. . 1995Cytokines and the nervous system. II. Actions and mechanisms of action. Trends Neurosci. 18, 130–136.doi:10.1016/0166-2236(95)93890-A (doi:10.1016/0166-2236(95)93890-A). Crossref, PubMed, ISI, Google Scholar - 111
Cunningham E. T.& De Souza E. B. . 1993Interleukin 1 receptors in the brain and endocrine tissues. Immunol. Today 14, 171–176.doi:10.1016/0167-5699(93)90282-P (doi:10.1016/0167-5699(93)90282-P). Crossref, PubMed, Google Scholar - 112
Sewards T. V.& Sewards M. . 2002Separate, parallel sensory and hedonic pathways in the mammalian somatosensory system. Brain Res. Bull. 58, 243–260. Crossref, PubMed, ISI, Google Scholar - 113
Sewards T. V. . 2004Dual separate pathways for sensory and hedonic aspects of taste. Brain Res. Bull. 62, 271–283.doi:10.1016/j.brainresbull.2003.10.004 (doi:10.1016/j.brainresbull.2003.10.004). Crossref, PubMed, ISI, Google Scholar - 114
Wicker B., Keysers C., Plailly J., Royet J. P., Gallese V.& Rizzolatti G. . 2003Both of us disgusted in my insula: the common neural basis of seeing and feeling disgust. Neuron 40, 655–664.doi:10.1016/S0896-6273(03)00679-2 (doi:10.1016/S0896-6273(03)00679-2). Crossref, PubMed, ISI, Google Scholar - 115
James W. . 1894The physical basis of emotions. Psychol. Rev. 1, 516–529.doi:10.1037/h0065078 (doi:10.1037/h0065078). Crossref, Google Scholar - 116
Ramirez-Amaya V., Alvarez-Borda B., Ormsby C. E., Martinez R. D., Perez-Montfort R.& Bermudez-Rattoni F. . 1996Insular cortex lesions impair the acquisition of conditioned immunosuppression. Brain Behav. Immunol. 10, 103–114.doi:10.1006/brbi.1996.0011 (doi:10.1006/brbi.1996.0011). Crossref, PubMed, ISI, Google Scholar - 117
Kipps C. M., Duggins A. J., McCusker E. A.& Calder A. J. . 2007Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington's disease. J. Cogn. Neurosci. 19, 1206–1217.doi:10.1162/jocn.2007.19.7.1206 (doi:10.1162/jocn.2007.19.7.1206). Crossref, PubMed, ISI, Google Scholar - 118
Pacheco-Lopez G., Niemi M. B., Engler H.& Schedlowski M. . 2007Behaviorally conditioned enhancement of immune responses. Psychoneuroimmunology, pp. 631–660,4th edn.Burlington, MA: Elsevier/Academic Press. Crossref, Google Scholar - 119
Espinosa E., Calderas T., Flores-Mucino O., Perez-Garcia G., Vazquez-Camacho A. C.& Bermudez-Rattoni F. . 2004Enhancement of antibody response by one-trial conditioning: contrasting results using different antigens. Brain Behav. Immun. 18, 76–80.doi:10.1016/S0889-1591(03)00108-9 (doi:10.1016/S0889-1591(03)00108-9). Crossref, PubMed, ISI, Google Scholar - 120
Dyck D. G., Janz L., Osachuk T. A., Falk J., Labinsky J.& Greenberg A. H. . 1990The Pavlovian conditioning of IL-1-induced glucocorticoid secretion. Brain Behav. Immun. 4, 93–104.doi:10.1016/0889-1591(90)90012-F (doi:10.1016/0889-1591(90)90012-F). Crossref, PubMed, ISI, Google Scholar - 121
Tazi A., Dantzer R., Crestani F.& Le Moal M. . 1988Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity. Brain Res. 473, 369–371.doi:10.1016/0006-8993(88)90868-2 (doi:10.1016/0006-8993(88)90868-2). Crossref, PubMed, ISI, Google Scholar - 122
Janz L. J., Brown R., Zuo L., Falk J., Greenberg A. H.& Dyck D. G. . 1991Conditioned taste aversion but not adrenal activity develops to ICV administration of interleukin-1 in rats. Physiol. Behav. 49, 691–694.doi:10.1016/0031-9384(91)90303-6 (doi:10.1016/0031-9384(91)90303-6). Crossref, PubMed, ISI, Google Scholar - 123
Bernstein I. L., Taylor E. M.& Bentson K. L. . 1991TNF-induced anorexia and learned food aversions are attenuated by area postrema lesions. Am. J. Physiol. 260, R906–R910. PubMed, ISI, Google Scholar - 124
Goehler L. E., Busch C. R., Tartaglia N., Relton J., Sisk D., Maier S. F.& Watkins L. R. . 1995Blockade of cytokine induced conditioned taste aversion by subdiaphragmatic vagotomy: further evidence for vagal mediation of immune-brain communication. Neurosci. Lett. 185, 163–166.doi:10.1016/0304-3940(95)11251-Q (doi:10.1016/0304-3940(95)11251-Q). Crossref, PubMed, ISI, Google Scholar - 125
Segall M. A.& Crnic L. S. . 1990A test of conditioned taste aversion with mouse interferon-alpha. Brain Behav. Immunol. 4, 223–231.doi:10.1016/0889-1591(90)90024-K (doi:10.1016/0889-1591(90)90024-K). Crossref, PubMed, ISI, Google Scholar - 126
Basso A. S., Pinto F. A., Russo M., Britto L. R., de Sa-Rocha L. C.& Palermo Neto J. . 2003Neural correlates of IgE-mediated food allergy. J. Neuroimmunol. 140, 69–77.doi:10.1016/S0165-5728(03)00166-8 (doi:10.1016/S0165-5728(03)00166-8). Crossref, PubMed, ISI, Google Scholar - 127
Cara D. C., Conde A. A.& Vaz N. M. . 1994Immunological induction of flavor aversion in mice. Braz. J. Med. Biol. Res. 27, 1331–1341. PubMed, ISI, Google Scholar - 128
Valles A., Marti O.& Armario A. . 2005Mapping the areas sensitive to long-term endotoxin tolerance in the rat brain: a c-fos mRNA study. J. Neurochem. 93, 1177–1188.doi:10.1111/j.1471-4159.2005.03100.x (doi:10.1111/j.1471-4159.2005.03100.x). Crossref, PubMed, ISI, Google Scholar - 129
Djuric V. J., Markovic B. M., Lazarevic M.& Jankovic B. D. . 1988Anaphylactic shock-induced conditioned taste aversion. II. Correlation between taste aversion and indicators of anaphylactic shock. Brain Behav. Immunol. 2, 24–31.doi:10.1016/0889-1591(88)90003-7 (doi:10.1016/0889-1591(88)90003-7). Crossref, PubMed, Google Scholar - 130
Pacheco-Lopez G., Espinosa E., Zamorano-Rojas H. M., Ramirez-Amaya V.& Bermudez-Rattoni F. . 2002Peripheral protein immunization induces rapid activation of the CNS, as measured by c-Fos expression. J. Neuroimmunol. 131, 50–59.doi:10.1016/S0165-5728(02)00264-3 (doi:10.1016/S0165-5728(02)00264-3). Crossref, PubMed, ISI, Google Scholar - 131
Markovic B. M., Djuric V. J., Lazarevic M.& Jankovic B. D. . 1988Anaphylactic shock-induced conditioned taste aversion. I. Demonstration of the phenomenon by means of three modes of CS-US presentation. Brain Behav. Immunol. 2, 11–23.doi:10.1016/0889-1591(88)90002-5 (doi:10.1016/0889-1591(88)90002-5). Crossref, PubMed, Google Scholar - 132
Elenkov I. J., Wilder R. L., Chrousos G. P.& Vizi E. S. . 2000The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol. Rev. 52, 595–638. PubMed, ISI, Google Scholar - 133
Elenkov I. J. . 2008Neurohormonal-cytokine interactions: implications for inflammation, common human diseases and well-being. Neurochem. Int. 52, 40–51.doi:10.1016/j.neuint.2007.06.037 (doi:10.1016/j.neuint.2007.06.037). Crossref, PubMed, ISI, Google Scholar - 134
Tracey K. J. . 2009Reflex control of immunity. Nat. Rev. Immunol. 9, 418–428.doi:10.1038/nri2566 (doi:10.1038/nri2566). Crossref, PubMed, ISI, Google Scholar - 135
Meisel C., Schwab J. M., Prass K., Meisel A.& Dirnagl U. . 2005Central nervous system injury-induced immune deficiency syndrome. Nat. Rev. Neurosci. 6, 775–786.doi:10.1038/nrn1765 (doi:10.1038/nrn1765). Crossref, PubMed, ISI, Google Scholar - 136
Ziemssen T.& Kern S. . 2007Psychoneuroimmunology—cross-talk between the immune and nervous systems. J. Neurol. 254((Suppl. 2)), II8–II11.doi:10.1007/s00415-007-2003-8 (doi:10.1007/s00415-007-2003-8). Crossref, PubMed, ISI, Google Scholar - 137
Sternberg E. M. . 2006Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat. Rev. Immunol. 6, 318–328.doi:10.1038/nri1810 (doi:10.1038/nri1810). Crossref, PubMed, ISI, Google Scholar - 138
Straub R. H. . 2004Complexity of the bi-directional neuroimmune junction in the spleen. Trends Pharmacol. Sci. 25, 640–646.doi:10.1016/j.tips.2004.10.007 (doi:10.1016/j.tips.2004.10.007). Crossref, PubMed, ISI, Google Scholar - 139
Tracey K. J. . 2002The inflammatory reflex. Nature 420, 853–859.doi:10.1038/nature01321 (doi:10.1038/nature01321). Crossref, PubMed, ISI, Google Scholar - 140
MacKenzie J. . 1886The production of the so-called rose effect by means of an artificial rose, with remarks and historical notes. Am. J. Med. Sci. 91, 45–57.doi:10.1097/00000441-188601000-00004 (doi:10.1097/00000441-188601000-00004). Crossref, Google Scholar - 141
Ikemi Y.& Nakagawa S. . 1962A psychosomatic study of contagious dermatitis. Kyushu J. Med. Sci. 13, 335–350. Google Scholar - 142
Dekker E., Pelser H.& Groen J. . 1957Conditioning as a cause of asthmatic attacks; a laboratory study. J. Psychosom. Res. 2, 97–108.doi:10.1016/0022-3999(57)90015-6 (doi:10.1016/0022-3999(57)90015-6). Crossref, PubMed, ISI, Google Scholar - 143
Gauci M., Husband A. J., Saxarra H.& King M. G. . 1994Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis. Physiol. Behav. 55, 823–825.doi:10.1016/0031-9384(94)90066-3 (doi:10.1016/0031-9384(94)90066-3). Crossref, PubMed, ISI, Google Scholar - 144
Smith G. R.& McDaniel S. M. . 1983Psychologically mediated effect on the delayed hypersensitivity reaction to tuberculin in humans. Psychosom. Med. 45, 65–70. Crossref, PubMed, ISI, Google Scholar - 145
Booth R. J., Petrie K. J.& Brook R. J. . 1995Conditioning allergic skin responses in humans: a controlled trial. Psychosom. Med. 57, 492–495. Crossref, PubMed, ISI, Google Scholar - 146
Bovbjerg D. . 2003Conditioning, cancer, and immune regulation. Brain Behav. Immunol. 17((Suppl. 1)), S58–S61.doi:10.1016/S0889-1591(02)00068-5 (doi:10.1016/S0889-1591(02)00068-5). Crossref, PubMed, ISI, Google Scholar - 147
Bovbjerg D. H., Redd W. H., Maier L. A., Holland J. C., Lesko L. M., Niedzwiecki D., Rubin S. C.& Hakes T. B. . 1990Anticipatory immune suppression and nausea in women receiving cyclic chemotherapy for ovarian cancer. J. Consult. Clin. Psychol. 58, 153–157.doi:10.1037/0022-006X.58.2.153 (doi:10.1037/0022-006X.58.2.153). Crossref, PubMed, ISI, Google Scholar - 148
Lekander M., Fürst C. J., Rotstein S., Blomgren H.& Fredrikson M. . 1995Anticipatory immune changes in women treated with chemotherapy for ovarian cancer. Int. J. Behav. Med. 2, 1–12.doi:10.1207/s15327558ijbm0201_1 (doi:10.1207/s15327558ijbm0201_1). Crossref, PubMed, ISI, Google Scholar - 149
Stockhorst U., Spennes-Saleh S., Körholz D., Göbel U., Schneider M. E., Steingrüber H. J.& Klosterhalfen S. . 2000Anticipatory symptoms and anticipatory immune responses in pediatric cancer patients receiving chemotherapy: features of a classically conditioned response?Brain Behav. Immun. 14, 198–218. Google Scholar - 150
Andrykowski M. A. . 1988Defining anticipatory nausea and vomiting: differences among cancer chemotherapy patients who report pretreatment nausea. J. Behav. Med. 11, 59–69.doi:10.1007/BF00846169 (doi:10.1007/BF00846169). Crossref, PubMed, ISI, Google Scholar - 151
Morrow G. R., Lindke J.& Black P. M. . 1991Anticipatory nausea development in cancer patients: replication and extension of a learning model. Br. J. Psychol. 82, 61–72.doi:10.1111/j.2044-8295.1991.tb02382.x (doi:10.1111/j.2044-8295.1991.tb02382.x). Crossref, PubMed, ISI, Google Scholar - 152
Matteson S., Roscoe J., Hickok J.& Morrow G. R. . 2002The role of behavioral conditioning in the development of nausea. Am. J. Obstet. Gynecol. 186((Suppl. 5 Understanding)), S239–S243.doi:10.1067/mob.2002.122597 (doi:10.1067/mob.2002.122597). Crossref, PubMed, ISI, Google Scholar - 153
Jacobsen P. B., Bovbjerg D. H.& Redd W. H. . 1993Anticipatory anxiety in women receiving chemotherapy for breast cancer. Health Psychol. 12, 469–475.doi:10.1037/0278-6133.12.6.469 (doi:10.1037/0278-6133.12.6.469). Crossref, PubMed, ISI, Google Scholar - 154
DiLorenzo T. A., Jacobsen P. B., Bovbjerg D. H., Chang H., Hudis C. A., Sklarin N. T.& Norton L. . 1995Sources of anticipatory emotional distress in women receiving chemotherapy for breast cancer. Ann. Oncol. 6, 705–711. Crossref, PubMed, ISI, Google Scholar - 155
Bovbjerg D. H., Montgomery G. H.& Raptis G. . 2005Evidence for classically conditioned fatigue responses in patients receiving chemotherapy treatment for breast cancer. J. Behav. Med. 28, 231–237.doi:10.1007/s10865-005-4659-9 (doi:10.1007/s10865-005-4659-9). Crossref, PubMed, ISI, Google Scholar - 156
Redd W. H., Dadds M. R., Futterman A. D., Taylor K. L.& Bovbjerg D. H. . 1993Nausea induced by mental images of chemotherapy. Cancer 72, 629–636.doi:10.1002/1097-0142(19930715)72:2<629::AID-CNCR2820720249>3.0.CO;2-7 (doi:10.1002/1097-0142(19930715)72:2<629::AID-CNCR2820720249>3.0.CO;2-7). Crossref, PubMed, ISI, Google Scholar - 157
Dadds M. R., Bovbjerg D. H., Redd W. H.& Cutmore T. R. . 1997Imagery in human classical conditioning. Psychol. Bull. 122, 89–103.doi:10.1037/0033-2909.122.1.89 (doi:10.1037/0033-2909.122.1.89). Crossref, PubMed, ISI, Google Scholar - 158
Buske-Kirschbaum A., Kirschbaum C., Stierle H., Lehnert H.& Hellhammer D. . 1992Conditioned increase of natural killer cell activity (NKCA) in humans. Psychosom. Med. 54, 123–132. Crossref, PubMed, ISI, Google Scholar - 159
Kirschbaum C., 1992Conditioning of drug-induced immunomodulation in human volunteers: a European collaborative study. Br. J. Clin. Psychol. 31, 459–472.doi:10.1111/j.2044-8260.1992.tb01019.x (doi:10.1111/j.2044-8260.1992.tb01019.x). Crossref, PubMed, ISI, Google Scholar - 160
Giang D. W., Goodman A. D., Schiffer R. B., Mattson D. H., Petrie M., Cohen N.& Ader R. . 1996Conditioning of cyclophosphamide-induced leukopenia in humans. J. Neuropsychiatr. Clin. Neurosci. 8, 194–201. Crossref, PubMed, ISI, Google Scholar - 161
Longo D. L., Duffey P. L., Kopp W. C., Heyes M. P., Alvord W. G., Sharfman W. H., Schmidt P. J., Rubinow D. R.& Rosenstein D. L. . 1999Conditioned immune response to interferon-gamma in humans. Clin. Immunol. 90, 173–181.doi:10.1006/clim.1998.4637 (doi:10.1006/clim.1998.4637). Crossref, PubMed, ISI, Google Scholar - 162
Goebel M. U., Hübell D., Kou W., Janssen O. E., Katsarava Z., Limmroth V.& Schedlowski M. . 2005Behavioral conditioning with interferon beta-1a in humans. Physiol. Behav. 84, 807–814.doi:10.1016/j.physbeh.2005.03.021 (doi:10.1016/j.physbeh.2005.03.021). Crossref, PubMed, ISI, Google Scholar - 163
Enck P., Benedetti F.& Schedlowski M. . 2008New insights into the placebo and nocebo responses. Neuron 59, 195–206.doi:10.1016/j.neuron.2008.06.030 (doi:10.1016/j.neuron.2008.06.030). Crossref, PubMed, ISI, Google Scholar - 164
Benedetti F., Carlino E.& Pollo A. . 2011How placebos change the patient's brain. Neuropsychopharmacology 36, 339–354.doi:10.1038/npp.2010.81 (doi:10.1038/npp.2010.81). Crossref, PubMed, ISI, Google Scholar - 165
Pacheco-Lopez G., Engler H., Niemi M. B.& Schedlowski M. . 2006Expectations and associations that heal: immunomodulatory placebo effects and its neurobiology. Brain Behav. Immunol. 20, 430–446.doi:10.1016/j.bbi.2006.05.003 (doi:10.1016/j.bbi.2006.05.003). Crossref, PubMed, ISI, Google Scholar - 166
Hotamisligil G. S. . 2006Inflammation and metabolic disorders. Nature 444, 860–867.doi:10.1038/nature05485 (doi:10.1038/nature05485). Crossref, PubMed, ISI, Google Scholar - 167
Chung S., Lapoint K., Martinez K., Kennedy A., Boysen Sandberg M.& McIntosh M. K. . 2006Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes. Endocrinology 147, 5340–5351.doi:10.1210/en.2006-0536 (doi:10.1210/en.2006-0536). Crossref, PubMed, ISI, Google Scholar - 168
Khazen W., M'Bika J. P., Tomkiewicz C., Benelli C., Chany C., Achour A.& Forest C. . 2005Expression of macrophage-selective markers in human and rodent adipocytes. FEBS Lett. 579, 5631–5634. Crossref, PubMed, ISI, Google Scholar - 169
Charriere G., Cousin B., Arnaud E., Andre M., Bacou F., Penicaud L.& Casteilla L. . 2003Preadipocyte conversion to macrophage. Evidence of plasticity. J. Biol. Chem. 278, 9850–9855.doi:10.1074/jbc.M210811200 (doi:10.1074/jbc.M210811200). Crossref, PubMed, ISI, Google Scholar - 170
Hotamisligil G. S.& Erbay E. . 2008Nutrient sensing and inflammation in metabolic diseases. Nat. Rev. Immunol. 8, 923–934.doi:10.1038/nri2449 (doi:10.1038/nri2449). Crossref, PubMed, ISI, Google Scholar - 171
Mifflin M. D., St Jeor S. T., Hill L. A., Scott B. J., Daugherty S. A.& Koh Y. O. . 1990A new predictive equation for resting energy expenditure in healthy individuals. Am. J. Clin. Nutr. 51, 241–247. Crossref, PubMed, ISI, Google Scholar - 172FAO/WHO/UNU. 1985Energy and protein requirements. Report of a joint FAO/WHO/UNU Expert Consultation. World Health Organ. Tech. Rep. Ser. 724, 1–206. PubMed, Google Scholar
- 173
Rassow J. . 2008Ernährung and verdauung. Biochemie, vol. 2 (ed.& Rassow J. ), pp. 184–200. Stuttgart, Germany: Thiemeaktualisierte Aufl. Google Scholar - 174
Magistretti P. . 2008Brain energy metabolism. Fundamental neuroscience (ed.& Squire L. ), pp. 217–293, 3rd edn.London, UK: Elsevier. Google Scholar - 175
Laughlin S. B.& Attwell D. . 2001The metabolic cost of neural information: from fly eye to mammalian cortex. Neuroenergetics: relevance for functional brain imaging (eds, Frackowiak R., Magistretti P., Shulman R., Altman J.& Adams M. ), pp. 54–65. Strasbourg, France: HFSP Press. Google Scholar - 176
Attwell D.& Laughlin S. B. . 2001An energy budget for signaling in the grey matter of the brain. J. Cereb. Blood Flow Metab. 21, 1133–1145.doi:10.1097/00004647-200110000-00001 (doi:10.1097/00004647-200110000-00001). Crossref, PubMed, ISI, Google Scholar - 177
Sokoloff L. . 1981Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J. Cereb. Blood Flow Metab. 1, 7–36.doi:10.1038/jcbfm.1981.4 (doi:10.1038/jcbfm.1981.4). Crossref, PubMed, ISI, Google Scholar - 178
Romanyukha A. A., Rudnev S. G.& Sidorov I. A. . 2006Energy cost of infection burden: an approach to understanding the dynamics of host–pathogen interactions. J. Theor. Biol. 241, 1–13.doi:10.1016/j.jtbi.2005.11.004 (doi:10.1016/j.jtbi.2005.11.004). Crossref, PubMed, ISI, Google Scholar - 179
Fox C. J., Hammerman P. S.& Thompson C. B. . 2005Fuel feeds function: energy metabolism and the T-cell response. Nat. Rev. Immunol. 5, 844–852.doi:10.1038/nri1710 (doi:10.1038/nri1710). Crossref, PubMed, ISI, Google Scholar - 180
Greiner E. F., Guppy M.& Brand K. . 1994Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. J. Biol. Chem. 269, 31 484–31 490. Crossref, ISI, Google Scholar - 181
Demas G. E., Chefer V., Talan M. I.& Nelson R. J. . 1997Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice. Am. J. Physiol. 273, R1631–R1637. PubMed, Google Scholar - 182
Browning R. C.& Kram R. . 2005Energetic cost and preferred speed of walking in obese versus normal weight women. Obes. Res. 13, 891–899.doi:10.1038/oby.2005.103 (doi:10.1038/oby.2005.103). Crossref, PubMed, Google Scholar - 183
Calder P. C. . 1995Fuel utilization by cells of the immune system. Proc. Nutr. Soc. 54, 65–82.doi:10.1079/PNS19950038 (doi:10.1079/PNS19950038). Crossref, PubMed, ISI, Google Scholar - 184
Maciver N. J., Jacobs S. R., Wieman H. L., Wofford J. A., Coloff J. L.& Rathmell J. C. . 2008Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J. Leukoc. Biol. 84, 949–957.doi:10.1189/jlb.0108024 (doi:10.1189/jlb.0108024). Crossref, PubMed, ISI, Google Scholar - 185
Schedlowski M., Hosch W., Oberbeck R., Benschop R. J., Jacobs R., Raab H. R.& Schmidt R. E. . 1996Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. J. Immunol. 156, 93–99. PubMed, ISI, Google Scholar - 186
Dhabhar F.& McEwen B. . 2001Bidirectional effects of stress and glucocorticoid hormones on immune function: possible explanations for paradoxical observations. Psychoneuroimmunology (ed.& Squire A. ), pp. 301–338,3rd edn.San Diego, CA: Academic Press. Google Scholar - 187
Born J., Lange T., Hansen K., Molle M.& Fehm H. L. . 1997Effects of sleep and circadian rhythm on human circulating immune cells. J. Immunol. 158, 4454–4464. PubMed, ISI, Google Scholar - 188
Lange T., Dimitrov S., Fehm H. L., Westermann J.& Born J. . 2006Shift of monocyte function toward cellular immunity during sleep. Arch. Intern. Med. 166, 1695–1700.doi:10.1001/archinte.166.16.1695 (doi:10.1001/archinte.166.16.1695). Crossref, PubMed, Google Scholar - 189
Merl V., 2004Preserved circadian rhythm of serum insulin concentration at low plasma glucose during fasting in lean and overweight humans. Metabolism 53, 1449–1453.doi:10.1016/j.metabol.2004.06.012 (doi:10.1016/j.metabol.2004.06.012). Crossref, PubMed, ISI, Google Scholar - 190
Wildenhoff K. E., Johansen J. P., Karstoft H., Yde H.& Sorensen N. S. . 1974Diurnal variations in the concentrations of blood acetoacetate and 3-hydroxybutyrate. The ketone body peak around midnight and its relationship to free fatty acids, glycerol, insulin, growth hormone and glucose in serum and plasma. Acta Med. Scand. 195, 25–28. Crossref, PubMed, Google Scholar - 191
Preston B. T., Capellini I., McNamara P., Barton R. A.& Nunn C. L. . 2009Parasite resistance and the adaptive significance of sleep. BMC Evol. Biol. 9, 7.doi:10.1186/1471-2148-9-7 (doi:10.1186/1471-2148-9-7). Crossref, PubMed, ISI, Google Scholar - 192
Lakatos J.& Harsagyi A. . 1988Serum total, HDL, LDL cholesterol, and triglyceride levels in patients with rheumatoid arthritis. Clin. Biochem. 21, 93–96.doi:10.1016/S0009-9120(88)80094-8 (doi:10.1016/S0009-9120(88)80094-8). Crossref, PubMed, ISI, Google Scholar - 193
Bruderlein H., Daniel R., Boismenu D., Julien N.& Couture F. . 1981Fatty acid profiles of serum phospholipids in patients suffering rheumatoid arthritis. Prog. Lipid Res. 20, 625–631.doi:10.1016/0163-7827(81)90117-X (doi:10.1016/0163-7827(81)90117-X). Crossref, PubMed, Google Scholar - 194
Iannello S., Cavaleri A., Milazzo P., Cantarella S.& Belfiore F. . 2003Low fasting serum triglyceride level as a precocious marker of autoimmune disorders. MedGenMed 5, 20. PubMed, Google Scholar - 195
Schenk S., Saberi M.& Olefsky J. M. . 2008Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest. 118, 2992–3002.doi:10.1172/JCI34260 (doi:10.1172/JCI34260). Crossref, PubMed, ISI, Google Scholar - 196
Hotamisligil G. S., Peraldi P., Budavari A., Ellis R., White M. F.& Spiegelman B. M. . 1996IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271, 665–668.doi:10.1126/science.271.5249.665 (doi:10.1126/science.271.5249.665). Crossref, PubMed, ISI, Google Scholar - 197
Sarzi-Puttini P., Atzeni F., Scholmerich J., Cutolo M.& Straub R. H. . 2006Anti-TNF antibody treatment improves glucocorticoid induced insulin-like growth factor 1 (IGF1) resistance without influencing myoglobin and IGF1 binding proteins 1 and 3. Ann. Rheum. Dis. 65, 301–305.doi:10.1136/ard.2005.040816 (doi:10.1136/ard.2005.040816). Crossref, PubMed, ISI, Google Scholar - 198
Frauwirth K. A.& Thompson C. B. . 2004Regulation of T lymphocyte metabolism. J. Immunol. 172, 4661–4665. Crossref, PubMed, ISI, Google Scholar - 199
tournier J. N., Hellmann A. Q., Lesca G., Jouan A., Drouet E.& Mathieu J. . 2003Fever-like thermal conditions regulate the activation of maturing dendritic cells. J. Leukoc. Biol. 73, 493–501.doi:10.1189/jlb.1002506 (doi:10.1189/jlb.1002506). Crossref, PubMed, ISI, Google Scholar - 200
Hanson D. F. . 1993Fever and the immune response. The effects of physiological temperatures on primary murine splenic T-cell responses in vitro. J. Immunol. 151, 436–448. PubMed, ISI, Google Scholar - 201
Imeri L.& Opp M. R. . 2009How (and why) the immune system makes us sleep. Nat. Rev. Neurosci. 10, 199–210.doi:10.1038/nrn2576 (doi:10.1038/nrn2576). Crossref, PubMed, ISI, Google Scholar - 202
Schaller M., Miller G. E., Gervais W. M., Yager S.& Chen E. . 2010Mere visual perception of other people's disease symptoms facilitates a more aggressive immune response. Psychol. Sci. 21, 649–652.doi:10.1177/0956797610368064 (doi:10.1177/0956797610368064). Crossref, PubMed, ISI, Google Scholar - 203
Stevenson R. J., Hodgson D., Oaten M. J., Barouei J.& Case T. I. . 2010The effect of disgust on oral immune function. Psychophysiology 48, 900–907.doi:10.1111/j.1469-8986.2010.01165.x (doi:10.1111/j.1469-8986.2010.01165.x). Crossref, PubMed, ISI, Google Scholar - 204
Stevenson R. J., Oaten M. J., Case T. I., Repacholi B. M.& Wagland P. . 2010Children's response to adult disgust elicitors: development and acquisition. Dev. Psychol. 46, 165–177.doi:10.1037/a0016692 (doi:10.1037/a0016692). Crossref, PubMed, ISI, Google Scholar - 205
Danovitch J.& Bloom P. . 2009Children's extension of disgust to physical and moral events. Emotion 9, 107–112.doi:10.1037/a0014113 (doi:10.1037/a0014113). Crossref, PubMed, ISI, Google Scholar - 206
Chapman H. A., Kim D. A., Susskind J. M.& Anderson A. K. . 2009In bad taste: evidence for the oral origins of moral disgust. Science 323, 1222–1226.doi:10.1126/science.1165565 (doi:10.1126/science.1165565). Crossref, PubMed, ISI, Google Scholar - 207
Lewis K. . 1998Pathogen resistance as the origin of kin altruism. J. Theor. Biol. 193, 359–363.doi:10.1006/jtbi.1998.0725 (doi:10.1006/jtbi.1998.0725). Crossref, PubMed, ISI, Google Scholar - 208
Restrepo D., Lin W., Salcedo E., Yamazaki K.& Beauchamp G. . 2006Odortypes and MHC peptides: complementary chemosignals of MHC haplotype?Trends Neurosci. 29, 604–609.doi:10.1016/j.tins.2006.08.001 (doi:10.1016/j.tins.2006.08.001). Crossref, PubMed, ISI, Google Scholar - 209
Thomas L. . 1975Symbiosis as an immunologic problem. The immune system and infectious diseases (eds, Neter E.& Milgrom F. ), pp. 2–11. Basel, Switzerland: Karger Verlag. Google Scholar


