Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-29T03:01:49.443Z Has data issue: false hasContentIssue false
  • English
  • Français

Sickness behavior, its mechanisms and significance

Published online by Cambridge University Press:  21 April 2008

Ian Tizard
Ian Tizard*
Affiliation:
Department of Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA
*
E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Recent studies have begun to clarify the pathogenesis of sickness behavior. Cytokines released by macrophages, dendritic cells and mast cells act on the brain to trigger behavioral changes in infected animals. The major cytokines, interleukin-1, tumor necrosis factor alpha, and others, all act on the hypothalamus to provoke alterations in the normal homeostatic condition. These include elevated body temperature, increased sleep, and loss of appetite as well as major alterations in lipid and protein metabolism leading to significant weight loss. Some of these changes are clearly directed towards enhancing the normal immune responses. The benefits of others such as appetite loss are unclear. It is also important to recognize that other animals may recognize sickness behavior as a sign of weakness and mark the victim out for targeting by predators. As a result, some prey species may work very hard to mask their sickness, a response that serves to complicate veterinary diagnosis.

Keywords

sicknessfevercachexiaanorexiacytokines
Type
Review Article
Information
Animal Health Research Reviews , Volume 9 , Issue 1 , June 2008 , pp. 87 - 99
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Banks, WA, Ortiz, L, Plotkin, SR and Kasin, AJ (1991). Human interleukin (IL)1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain by a shared saturable mechanism. Journal of Pharmacology and Experimental Therapeutics 259: 988–996.Google ScholarPubMed
Barksby, HE, Lea, SR, Preshaw, PM and Taylor, JJ (2007). The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clinical and Experimental Immunology 149: 217–225.CrossRefGoogle ScholarPubMed
Bazar, KA, Yun, AJ and Lee, PY (2005). ‘Starve a fever and feed a cold’: feeding and anorexia may be adaptive behavioral modulators of autonomic and T helper balance. Medical Hypotheses 64: 1080–1084.CrossRefGoogle Scholar
Beutler, B and Cerami, A (1986). Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature 320: 584–588.CrossRefGoogle ScholarPubMed
Biddle, C (2006). The neurobiology of the human febrile response. American Association of Nurse Anesthetists Journal 74: 145–150.Google ScholarPubMed
Bonaldi, T, Talamo, F, Scaffidi, P, Ferrera, D, Porto, A, Bachi, A, Rubartelli, A, Agresi, A and Bianchi, ME (2003). Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. European Molecular Biology Organization Journal 22: 5551–5560.CrossRefGoogle ScholarPubMed
Bradford, CD, Cotter, JD, Thorburn, MS, Walker, RJ and Gerrard, DF (2007). Exercise can be pyrogenic in humans. American Journal of Physiology, Regulatory, Integrative and Comparative Physiology 292: R143–149.CrossRefGoogle ScholarPubMed
Breder, CD, Tsujimoto, M, Terano, Y, Scott, DW and Saper, CB (1993). Distribution and characterization of tumor necrosis factor-alpha-like immunoreactivity in the murine central nervous system. Journal of Comparative Neurology 337: 543–567.CrossRefGoogle ScholarPubMed
Breder, CD, Hazuka, C, Ghayur, T, Klug, C, Huginin, M, Yasuda, K, Teng, M and Saper, CB (1994). Regional induction of tumor necrosis factor alpha expression in the mouse after systemic lipopolysaccharide administration. Proceedings of the National Academy of Sciences USA 91: 11393–11397.CrossRefGoogle ScholarPubMed
Bryant, PA, Trinder, J and Curtis, N (2004). Sick and tired: does sleep have a vital role in the immune system? Nature Reviews, Immunology 4: 457–467.CrossRefGoogle ScholarPubMed
Carmichael, LE and Barnes, FD (1969). Effect of temperature on growth of canine herpesvirus in canine kidney cell and macrophage cultures. Journal of Infectious Disease 120: 664–668.CrossRefGoogle ScholarPubMed
Cartmell, T, Ball, C, Bristow, AF, Mitchell, D and Poole, S (2003). Endogenous interleukin-10 is required for the defervescence of fever induced by local lipopolysaccharide-induced and Staphyloccus aureus-induced inflammation in rats. Journal of Physiology 549: 653–664.CrossRefGoogle Scholar
Cartmell, T, Luheshi, GN and Rothwell, NJ (1999). Brain sites of action of endogenous interleukin-1 in the febrile response to localized inflammation in the rat. Journal of Physiology 518: 585–594.CrossRefGoogle ScholarPubMed
Cavadini, G, Petrzilka, S, Kohler, P, Jud, C, Tobler, I, Birchler, T and Fontana, A (2007). TNF-α suppresses the expression of clock genes by interfering with E-box-mediated transcription. Proceedings of the National Academy of Sciences USA 104: 12843–12848.CrossRefGoogle ScholarPubMed
Cheema, MA, Qureshi, MA and Havenstein, GB (2003). A comparison of the immune response of a 2001 commercial broiler with a 1957 randombred broiler strain when frd representative 1957 and 2001 broiler diets. Poultry Science 82: 1519–1529.CrossRefGoogle Scholar
Chen, Q, Carroll, HP and Gadina, M (2006). The newest interleukins: recent additions to the ever-growing cytokine family. Vitamins and Hormones 74: 207–228.CrossRefGoogle Scholar
Chen, Q, Fisher, DT, Kucinska, SA, Wang, WC and Evans, SS (2006). Dynamic control of lymphocyte trafficking by fever-range thermal stress. Cancer Immunology and Immunotherapy 55: 299–311.CrossRefGoogle ScholarPubMed
Conti, B, Sanchez-Alavez, M, Winsky-Sommerer, R, Morale, MC, Lucero, J, Brownell, S, Fabre, V, Huitron-Resendiz, S, Henriksen, S, Zorrilla, EP, de Lecea, L and Bartfai, T (2006). Transgenic mice with a reduced core body temperature have an increased life-span. Science 314: 825–828.CrossRefGoogle ScholarPubMed
Conti, B, Tabarean, I, Andrei, C and Bartfai, T (2004). Cytokines and fever. Frontiers in Bioscence 9: 1433–1449.CrossRefGoogle ScholarPubMed
Crimmins, EM and Finch, CE (2006). Infection, inflammation, height and longevity. Proceedings of the National Academy of Sciences USA 103: 498–503.CrossRefGoogle ScholarPubMed
Darsaud, A, Bourdon, L, Mercier, S, Chapotot, F, Bouteille, B, Cespuglio, R and Buguet, A (2004). Twenty-four-hour disruption of the sleep-wake cycle and sleep-onset REM-like episodes in a rat model of African trypanosomiasis. Sleep 27: 42–46.CrossRefGoogle Scholar
Darko, DF, Miller, JC, Gallen, C, White, J, Koziol, J, Brown, SJ, Hayduk, R, Atkinson, JH, Assmus, J, Munnell, DT, Naitoh, P, McCutchan, JA and Mitler, MM (1995). Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection. Proceedings of the National Academy of Sciences USA 92: 12080–12084.CrossRefGoogle ScholarPubMed
Del Rey, A, Besedovsky, HO, Sorkin, E, de Prada, M and Arrenbrecht, S (1981). Immunoregulation mediated by the sympathetic nervous system II. Cellular Immunology 63: 329–334.CrossRefGoogle ScholarPubMed
Dinarello, CA (2006). Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. American Journal of Clinical Nutrition 83 (suppl): 447S–455S.CrossRefGoogle ScholarPubMed
Dofferhoff, AS, Vellenga, E, Limburg, PC, van Zanten, A, Mulder, PO and Weits, J (1991). Tumour necrosis factor (cachectin) and other cytokines in septic shock: a review of the literature. The Netherlands Journal of Medicine 39: 45–62.Google ScholarPubMed
Dumitriu, IE, Baruah, P, Manfredi, AA, Bianchi, ME and Rovere-Querini, P (2005). HMGB1: guiding immunity from within. Trends in Immunology 26: 381–387.CrossRefGoogle Scholar
Dunn, AJ and Swiergiel, AH (1998). The role of cytokines in infection-related behavior. Annals of the New York Academy of Sciences 840: 577–585.CrossRefGoogle ScholarPubMed
Dunn, AJ and Swiergiel, AH (2000). The role of cyclooxygenases in enndotooxin- and interleukin-1-induced hypophagia. Brain, Behavior and Immunity 14: 141–152.CrossRefGoogle ScholarPubMed
Eiseman, B, Mallette, WG, Wotkyns, RS, Summers, WB and Tong, JL (1956). Prolonged hypothermia in experimental pneumococcal peritonitis. Journal of Clinical Invesigation 35: 940–946.CrossRefGoogle ScholarPubMed
Elenkov, IJ, Iezzoni, DG, Daly, A, Harris, AG and Chrousos, GP (2005). Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12: 255–269.CrossRefGoogle ScholarPubMed
Elenkov, IJ, Wilder, RL, Chrousos, GP and Vizi, ES (2000). The sympathetic nerve – an integrative interface between two ‘supersystems’, the brain and the immune system. Pharmacological Review 52: 1–44.Google ScholarPubMed
Faina, JN (2006). Release of Interleukins and Other Inflammatory Cytokines by Human Adipose Tissue Is Enhanced in Obesity and Primarily due to the Nonfat Cells. Vitamins and Hormones 74: 443–477.CrossRefGoogle Scholar
Feng, J, Wang, Y and Krueger, JM (1997). Mice lacking the TNF 55 kDa receptor fail to sleep more after TNFa treatment. Neuroscience 17: 5949–5955.CrossRefGoogle Scholar
Feng, J, Wang, Y and Krueger, JM (1998). Effects of interleukin-1β on sleep are mediated by the type 1 receptor. American Journal of Physiology 274: R655–R660.Google Scholar
Francis, K, Lewis, BM, Akatsu, H, Monk, PN, Cain, SA, Scanlon, MF, Morgan, BP, Ham, J and Gasque, P (2003). Complement C3a receptors in the pituitary gland: a novel pathway by which an innate immune molecule releases hormones involved in the control of inflammation. The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 17: 2266–2268.CrossRefGoogle ScholarPubMed
Friedman, EM, Hayney, MS, Love, GD, Urry, HL, Rosenkranz, MA, Davidson, RJ, Singer, BH and Ryff, CD (2005). Social relationships, sleep quality and interleukin 6 in aging women. Proceedings of the National Academy of Sciences USA 102: 18757–18762.CrossRefGoogle ScholarPubMed
Furuuchi, S and Shimmizu, Y (1976). Effect of ambient temperatures on multiplication of attenuated transmissible gastroenteritis virus in the bodies of newborn piglets. Infection and Immunity 13: 990–992.CrossRefGoogle ScholarPubMed
Gabay, C and Kushner, I (1999). Acute-phase proteins and other systemic responses to inflammation. New England Journal of Medicine 340: 448–454.CrossRefGoogle ScholarPubMed
Hansen, M and JM, Krueger (1997). Subdiaphragmatic vagotomy blocks the sleep and fever-promoting effects of interleukin-1β. American Journal of Physiology 42: R1246–R1253.Google Scholar
Harris, HE and Andersson, U (2004). The nuclear protein HMGB1 as a proinflammatory mediator. European Journal of Immunology 34: 1503–1512.CrossRefGoogle Scholar
Heller, HC and Ruby, NF (2004). Sleep and circadian rhythms in mammalian torpor. Annual Review of Physiology 66: 275–289.CrossRefGoogle ScholarPubMed
Hermann, GE, Holmes, GM and Rogers, RC (2005). TNF-a modulation of visceral and spinal sensory processing. Current Pharmaceutical Design 11: 1391–1409.CrossRefGoogle Scholar
Hermann, GE and Rogers, RC (2008). TNF-alpha: A trigger of autonomic dysfunction. Neuroscience 14: 53–67.Google ScholarPubMed
Hogan, D, Morrow, JD, Smith, EM and Opp, MR (2003). Interleukin-6 alters sleep in rats. Journal of Neuroimmunology 137: 59–66.CrossRefGoogle Scholar
Harden, LM, du Plessis, I, Poole, S and Laburn, HP (2006). Interleukin-6 and leptin mediate lipopolysaccharide-induced fever and sickness behavior. Physiology and Behaviour 89: 146–155.CrossRefGoogle ScholarPubMed
Hawiger, J (2001). Innate immunity and inflammation: A transcriptional paradigm. Immunologic Research 23: 99–110.CrossRefGoogle ScholarPubMed
Horne, JA (1988). Why we sleep – The functions of sleep in humans and other mammals. Oxford: Oxford University Press, p. 320.Google Scholar
Irwin, MR and Miller, AH (2007). Depressive disorders and immunity: 20 years of progress and discovery. Brain, Behavior and Immunity 21: 374–383.CrossRefGoogle ScholarPubMed
Johnson, RW (2002). The concept of sickness behavior: a brief chronological account of four key discoveries. Veterinary Immunology and Immunopathology 87: 443–450.CrossRefGoogle ScholarPubMed
Jones, SA (2005). Directing transition from innate to acquired immunity: defining a role for IL-6. Journal of Immunology 175: 3463–3468.CrossRefGoogle ScholarPubMed
Kahl, KG, Kruse, N, Rieckmann, P and Schmidt, MH (2004). Cytokine mRNA expression patterns in the disease course of female adolescents with anorexia nervosa. Psychoneuroendocrinology 29: 13–20.CrossRefGoogle ScholarPubMed
Kim, YW, Kim, KH, Ahn, DK, Kim, HS, Kim, JY, Lee, DC and Park, SY (2007). Time-course changes of hormones and cytokines by lipopolysaccharide and its relation with anorexia. Journal of Physiological Sciences 57: 159–165.CrossRefGoogle ScholarPubMed
Kin, NW and Sanders, VM (2006). It takes nerve to tell T and B cells what to do. Journal of Leukocyte Biology 79: 1093–1094.CrossRefGoogle Scholar
Krauchi, K (2007). The human sleep-wake cycle reconsidered from a thermoregulatory point of view. Physiology and Behaviour 90: 236–245.CrossRefGoogle ScholarPubMed
Krueger, MJ and Madje, JA (1994). Microbial products and cytokines in sleep and fever regulation. Critical Reviews in Immunology 14: 355–379.CrossRefGoogle ScholarPubMed
Krueger, MJ and Majde, JA (2003). Humoral links between sleep and the immune system: research issues. Annals of the New York Academy of Sciences 992: 9–20.CrossRefGoogle ScholarPubMed
Krueger, MJ, Ringler, DH and Anver, MR (1975). Fever and survival. Science 188: 166–168.Google Scholar
Krueger, MJ (1991). Fever: Role of pyrogens and cryogens. Physiological Reviews 71: 93–127.Google Scholar
Krueger, JM, Fang, J, Taishi, P, Chen, Z, Kushikata, T and Gardi, J (1998). Sleep: a physiologic role for IL-1β and TNF-a. Annals of the New York Academy of Sciences 856: 148–159.CrossRefGoogle Scholar
Kubota, T, Kushikata, T, Feng, J and Krueger, JM (2000). Nuclear factor-kB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep. American Journal of Physiology 279: R404–R413.Google Scholar
Lotze, MT and Tracey, KJ (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nature Reviews, Immunology 5: 331–342.CrossRefGoogle ScholarPubMed
Mackowiak, PA (1994). Fever: Blessing or curse? A unifying hypothesis. Annals of Internal Medicine 120: 1037–1040.CrossRefGoogle ScholarPubMed
Melstrom, LG, Melstrom, KA, Ding, X-Z and Adrian, TE (2007). Mechanisms of skeletal muscle degradation and its therapy in cancer cachexia. Histology and Histopathology 22: 805–814.Google ScholarPubMed
Mitch, WE and Goldberg, AL (1996). Mechanisms of muscle wasting, the role of the ubiquitin-proteasome pathway. New England Journal of Medicine 335: 1897–1905.CrossRefGoogle ScholarPubMed
Mullington, JM, Hinze-Selch, D and Pollmacher, T (2001). Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions. Annals of the New York Academy of Sciences 933: 201–210.CrossRefGoogle ScholarPubMed
Murray, MJ and Murray, AB (1979). Anorexia of infection as a mechanism of host defense. American Journal of Clinical Nutrition 32: 593–596.CrossRefGoogle ScholarPubMed
Opp, MR, Obal, F and Krueger, JM (1991). Interleukin-1 alters rat sleep: Temporal and dose related effects. American Journal of Physiology 260: R52–R58.Google ScholarPubMed
Opp, MR, Smith, EM and Hughes, TK Jr (1995). Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system to reduce sleep. Journal of Neuroimmunology 60: 165–168.CrossRefGoogle ScholarPubMed
Pollard, LC, Choy, EH, Gonzalez, J, Khoshaba, B and Scott, DL (2006). Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology 45: 885–889.CrossRefGoogle Scholar
Popa, C, Netea, G, van Riel, PLCM, van der Meer, JW and Stalenhoef, AF (2007). The role of TNFα in chronic inflammatory conditions, intermediary metabolism and cardiovascular risk. Journal of Lipid Research 48: 751–762.CrossRefGoogle ScholarPubMed
Pritchard, MT, Li, Z and Repasky, EA (2005). Nitric oxide production is regulated by fever-range thermal stimulation of murine macrophages. Journal of Leukocyte Biology 78: 630–638.CrossRefGoogle ScholarPubMed
Quan, N, Zhang, Z, Emery, M, Bonsall, R and Weiss, JM (1996). Detection of interleukin-1 bioactivity in various brain regions of normal healthy rats. Neuroimmunomodulation 3: 47–55.CrossRefGoogle ScholarPubMed
Quan, N, Whiteside, M and Herkenham, M (1998). Time course and localization patterns of interleukin-1β messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience 83: 281–293.CrossRefGoogle ScholarPubMed
Reid, MB and Li, YP (2001). Tumor necrosis factor-alpha and muscle wasting. Respiratory Research 2: 269–272.CrossRefGoogle ScholarPubMed
Roth, J, Rummel, C, Barth, SW, Gerstberger, R and Hubschle, T (2006). Molecular aspects of fever and hyperthermia. Neurologic Clinics 24: 421–439.CrossRefGoogle ScholarPubMed
Rothwell, NJ and Luheshi, GN (2000). Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends in Neuroscience 23: 618–625.CrossRefGoogle ScholarPubMed
Sakami, S, Ishikawa, T, Kawakami, N, Haratani, T, Fukui, A, Kobayashi, F, Fujita, O, Araki, S and Kawamura, N (2002–2003). Coemergence of insomnia and a shift in the Th1/Th2 balance toward Th2 dominance. Neuroimmunomodulation 10: 337–343.CrossRefGoogle Scholar
Sandig, H, McDonald, J, Gilmour, J, Arno, M, Lee, TH and Cousins, DJ (2007). Human Th2 cells selectively express the orexigenic peptide, pro-melanin concentrating hormone. Proceedings of the National Academy of Sciences USA 104: 12440–12444.CrossRefGoogle ScholarPubMed
Sharshar, T, Hopkinson, NS, Orlikowski, D and Annane, D (2005). Science review: the brain in sepsis–culprit and victim. Critical Care 9: 37–44.CrossRefGoogle ScholarPubMed
Shohem, S, Ahokas, RA, Blettele, CM and Krueger, JM (1987). Effect of muramyl dipeptide on sleep, body temperature and plasma copper after intracerebral ventricular administration. Brain Research 419: 223–226.CrossRefGoogle Scholar
Spriggs, DR, Sherman, ML, Michie, H, Arthur, KA, Imamura, K, Wilmore, D, Frei, E 3rd and Kufe, DW (1988). Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study. Journal of the National Cancer Institute 80: 1039–1044.CrossRefGoogle ScholarPubMed
Steinman, L (2004). Elaborate interactions between the immune and nervous systems. Nature Immunology 5: 575–581.CrossRefGoogle ScholarPubMed
Sternberg, EM (1997). Neural-immune interactions in health and disease. Journal of Clinical Investigation 100: 2641–2647.CrossRefGoogle ScholarPubMed
Swiergiel, AH and Dunn, AJ (2002). Distinct roles for cyclooxygenases 1 and 2 in interleukin-1-induced behavioral changes. Journal of Pharmacology and Experimental Therapeutics 302: 1031–1036.CrossRefGoogle ScholarPubMed
Swiergiel, AH and Dunn, AJ (2006). Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice. Behavioural Brain Research 171: 94–108CrossRefGoogle Scholar
Szelényi, J (2001). Cytokines and the central nervous system. Brain Research Bulletin 54: 329–338.CrossRefGoogle ScholarPubMed
Szelenyi, Z and Szekely, M (2004). Sickness behavior in fever and hypothermia. Frontiers in Bioscience 9: 2447–2456.CrossRefGoogle ScholarPubMed
Takehashi, S, Kepes, L, Fang, J and Krueger, JM (1995). An anti-tumor necrosis factor antibody suppresses sleep in rats and rabbits. Brain Research 690: 241–244.CrossRefGoogle Scholar
Toth, LA and Krueger, JM (1988). Alteration of sleep in rabbits by Staphylococcus aureus infection. Infection and Immunity 56: 1785–1791.CrossRefGoogle ScholarPubMed
Toth, LA, Tolley, EA and Krueger, JM (1993). Sleep as a prognostic indicator during infectious diseases in rabbits. Proceedings of the Society for Experimental Biology and Medicine 203: 179–192.CrossRefGoogle Scholar
Tracey, KJ (2007). Physiology and immunology of the cholinergic antiinflammatory pathway. Journal of Clinical Investigation 117: 289–296.CrossRefGoogle ScholarPubMed
Vaugn, LK, Bernheim, HA and Kluger, MJ (1974). Fever in a lizard Dipsosaurus dorsalis. Nature 252: 473–474.CrossRefGoogle Scholar
van den Top, M and Spanswick, D (2006). Integration of metabolic stimuli in the hypothalamic arcuate nucleus. Progress in Brain Research 153: 141–154.CrossRefGoogle ScholarPubMed
Vizi, ES, Orso, E, Osipenko, ON, Hasko, G and Elenkov, IJ (1995). Neurochemical, electrophysiological, and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes. Neuroscience 68: 1263–1276.CrossRefGoogle ScholarPubMed
Watkins, LR, Maier, SF and Goehler, LE (1995). Cytokine-to-brain communication: A review and analysis of alternative mechanisms. Life Sciences 57: 1011–1026.CrossRefGoogle ScholarPubMed
Weisberg, SP, McCann, D, Desai, M, Rosenbaum, M, Leibel, RL and Ferrante, AW Jr (2003). Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112: 1796–1808.CrossRefGoogle ScholarPubMed
Welter, JS, Meyers, P and Krueger, M (1989). Microinjection of interleukin-1 into brain: separation of sleep and fever responses. Physiology and Behaviour 45: 169–176.CrossRefGoogle Scholar
Wrona, D (2006). Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. Journal of Neuroimmunology 172: 38–58.CrossRefGoogle ScholarPubMed
Wen, JC and Prendergast, BJ (2007). Photoperiodic regulation of behavioral responsiveness to proinflammatory cytokines. Physiology and Behaviour 90: 717–725.CrossRefGoogle ScholarPubMed
Zorilla, EP, Sanchez-Alavez, M, Sugama, S, Brennan, M, Fernandez, R, Bartfai, T and Conti, B (2007). Interleukin 18 controls energy homeostasis by suppressing appetite and feed efficiency. Proceedings of the National Academy of Sciences USA 104: 11097–11102.CrossRefGoogle Scholar