Abstract
Symptoms of infection, such as fever, anorexia and lethargy, are ubiquitous among vertebrates. Rather than nonspecific manifestations of illness, these responses are organized, adaptive strategies that are often critical to host survival. During times of energetic shortage such as winter, however, it may be detrimental for individuals to prolong energetically demanding symptoms such as fever. Individuals may adjust their immune responses prior to winter by using day length to anticipate energetically-demanding conditions. If the expression of sickness behaviours is constrained by energy availability, then cytokine production, fever, and anorexia should be attenuated in infected Siberian hamsters housed under simulated winter photoperiods. We housed hamsters in either long (14 L : 10 D) or short (10 L : 14 D) day lengths and assessed cytokines, anorexia and fever following injections of lipopolysaccharide (LPS). Short days attenuated the response to lipopolysaccharide, by decreasing the production of interleukin (IL)-6 and IL-1beta, and diminishing the duration of fever and anorexia. Short-day exposure in hamsters also decreased the ingestion of dietary iron, a nutrient vital to bacterial replication. Taken together, short day lengths attenuated the symptoms of infection, presumably to optimize energy expenditure and survival outcome.
Full Text
The Full Text of this article is available as a PDF (249.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ardawi M. S., Newsholme E. A. Metabolism in lymphocytes and its importance in the immune response. Essays Biochem. 1985;21:1–44. [PubMed] [Google Scholar]
- Aubert A., Goodall G., Dantzer R. Compared effects of cold ambient temperature and cytokines on macronutrient intake in rats. Physiol Behav. 1995 May;57(5):869–873. doi: 10.1016/0031-9384(94)00391-h. [DOI] [PubMed] [Google Scholar]
- Aubert A., Goodall G., Dantzer R., Gheusi G. Differential effects of lipopolysaccharide on pup retrieving and nest building in lactating mice. Brain Behav Immun. 1997 Jun;11(2):107–118. doi: 10.1006/brbi.1997.0485. [DOI] [PubMed] [Google Scholar]
- Aubert A. Sickness and behaviour in animals: a motivational perspective. Neurosci Biobehav Rev. 1999 Nov;23(7):1029–1036. doi: 10.1016/s0149-7634(99)00034-2. [DOI] [PubMed] [Google Scholar]
- Avitsur R., Yirmiya R. The immunobiology of sexual behavior: gender differences in the suppression of sexual activity during illness. Pharmacol Biochem Behav. 1999 Dec;64(4):787–796. doi: 10.1016/s0091-3057(99)00165-3. [DOI] [PubMed] [Google Scholar]
- Bartness T. J., Powers J. B., Hastings M. H., Bittman E. L., Goldman B. D. The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? J Pineal Res. 1993 Nov;15(4):161–190. doi: 10.1111/j.1600-079x.1993.tb00903.x. [DOI] [PubMed] [Google Scholar]
- Bilbo S. D., Nelson R. J. Sex steroid hormones enhance immune function in male and female Siberian hamsters. Am J Physiol Regul Integr Comp Physiol. 2001 Jan;280(1):R207–R213. doi: 10.1152/ajpregu.2001.280.1.R207. [DOI] [PubMed] [Google Scholar]
- Cabantchik Z. I., Moody-Haupt S., Gordeuk V. R. Iron chelators as anti-infectives; malaria as a paradigm. FEMS Immunol Med Microbiol. 1999 Dec;26(3-4):289–298. doi: 10.1111/j.1574-695X.1999.tb01401.x. [DOI] [PubMed] [Google Scholar]
- Dantzer R., Bluthé R. M., Gheusi G., Cremona S., Layé S., Parnet P., Kelley K. W. Molecular basis of sickness behavior. Ann N Y Acad Sci. 1998 Sep 29;856:132–138. doi: 10.1111/j.1749-6632.1998.tb08321.x. [DOI] [PubMed] [Google Scholar]
- Dantzer R., Bluthé R. M., Layé S., Bret-Dibat J. L., Parnet P., Kelley K. W. Cytokines and sickness behavior. Ann N Y Acad Sci. 1998 May 1;840:586–590. doi: 10.1111/j.1749-6632.1998.tb09597.x. [DOI] [PubMed] [Google Scholar]
- Deacon S., Arendt J. Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res. 1995 Aug 7;688(1-2):77–85. doi: 10.1016/0006-8993(95)96872-i. [DOI] [PubMed] [Google Scholar]
- Deen CM, Hutchison VH. Effects of lipopolysaccharide and acclimation temperature on induced behavioral fever in juvenile Iguana iguana. J Therm Biol. 2001 Feb 1;26(1):55–63. doi: 10.1016/s0306-4565(00)00026-7. [DOI] [PubMed] [Google Scholar]
- Demas G. E., Chefer V., Talan M. I., Nelson R. J. Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice. Am J Physiol. 1997 Nov;273(5 Pt 2):R1631–R1637. doi: 10.1152/ajpregu.1997.273.5.R1631. [DOI] [PubMed] [Google Scholar]
- Demas G. E., Nelson R. J. Exogenous melatonin enhances cell-mediated, but not humoral, immune function in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms. 1998 Jun;13(3):245–252. doi: 10.1177/074873098129000084. [DOI] [PubMed] [Google Scholar]
- Drazen D. L., Klein S. L., Yellon S. M., Nelson R. J. In vitro melatonin treatment enhances splenocyte proliferation in prairie voles. J Pineal Res. 2000 Jan;28(1):34–40. doi: 10.1034/j.1600-079x.2000.280105.x. [DOI] [PubMed] [Google Scholar]
- Dunn A. J., Swiergiel A. H. The role of cytokines in infection-related behavior. Ann N Y Acad Sci. 1998 May 1;840:577–585. doi: 10.1111/j.1749-6632.1998.tb09596.x. [DOI] [PubMed] [Google Scholar]
- Exton M. S. Infection-induced anorexia: active host defence strategy. Appetite. 1997 Dec;29(3):369–383. doi: 10.1006/appe.1997.0116. [DOI] [PubMed] [Google Scholar]
- Gomes M. S., Dom G., Pedrosa J., Boelaert J. R., Appelberg R. Effects of iron deprivation on Mycobacterium avium growth. Tuber Lung Dis. 1999;79(5):321–328. doi: 10.1054/tuld.1999.0216. [DOI] [PubMed] [Google Scholar]
- Hart B. L. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988 Summer;12(2):123–137. doi: 10.1016/s0149-7634(88)80004-6. [DOI] [PubMed] [Google Scholar]
- Heideman P. D., Bronson F. H. Photoperiod, melatonin secretion, and sexual maturation in a tropical rodent. Biol Reprod. 1990 Nov;43(5):745–750. doi: 10.1095/biolreprod43.5.745. [DOI] [PubMed] [Google Scholar]
- Hershko C., Gordeuk V. R., Thuma P. E., Theanacho E. N., Spira D. T., Hider R. C., Peto T. E., Brittenham G. M. The antimalarial effect of iron chelators: studies in animal models and in humans with mild falciparum malaria. J Inorg Biochem. 1992 Aug 15;47(3-4):267–277. doi: 10.1016/0162-0134(92)84072-u. [DOI] [PubMed] [Google Scholar]
- Hoen B. Iron and infection: clinical experience. Am J Kidney Dis. 1999 Oct;34(4 Suppl 2):S30–S34. doi: 10.1053/AJKD034s00030. [DOI] [PubMed] [Google Scholar]
- Husband A. J. The immune system and integrated homeostasis. Immunol Cell Biol. 1995 Aug;73(4):377–382. doi: 10.1038/icb.1995.58. [DOI] [PubMed] [Google Scholar]
- Illnerová H., Hoffmann K., Vanecek J. Adjustment of pineal melatonin and N-acetyltransferase rhythms to change from long to short photoperiod in the Djungarian hamster Phodopus sungorus. Neuroendocrinology. 1984 Mar;38(3):226–231. doi: 10.1159/000123895. [DOI] [PubMed] [Google Scholar]
- Inui A. Transgenic approach to the study of body weight regulation. Pharmacol Rev. 2000 Mar;52(1):35–61. [PubMed] [Google Scholar]
- Kent S., Bluthé R. M., Kelley K. W., Dantzer R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci. 1992 Jan;13(1):24–28. doi: 10.1016/0165-6147(92)90012-u. [DOI] [PubMed] [Google Scholar]
- Kluger M. J., Kozak W., Conn C. A., Leon L. R., Soszynski D. Role of fever in disease. Ann N Y Acad Sci. 1998 Sep 29;856:224–233. doi: 10.1111/j.1749-6632.1998.tb08329.x. [DOI] [PubMed] [Google Scholar]
- Kluger M. J., Rothenburg B. A. Fever and reduced iron: their interaction as a host defense response to bacterial infection. Science. 1979 Jan 26;203(4378):374–376. doi: 10.1126/science.760197. [DOI] [PubMed] [Google Scholar]
- Langhans W. Anorexia of infection: current prospects. Nutrition. 2000 Oct;16(10):996–1005. doi: 10.1016/s0899-9007(00)00421-4. [DOI] [PubMed] [Google Scholar]
- Lennie T. A. Relationship of body energy status to inflammation-induced anorexia and weight loss. Physiol Behav. 1998 Jun 15;64(4):475–481. doi: 10.1016/s0031-9384(98)00103-6. [DOI] [PubMed] [Google Scholar]
- Liebmann P. M., Wölfler A., Felsner P., Hofer D., Schauenstein K. Melatonin and the immune system. Int Arch Allergy Immunol. 1997 Mar;112(3):203–211. doi: 10.1159/000237455. [DOI] [PubMed] [Google Scholar]
- Luheshi G. N., Gardner J. D., Rushforth D. A., Loudon A. S., Rothwell N. J. Leptin actions on food intake and body temperature are mediated by IL-1. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):7047–7052. doi: 10.1073/pnas.96.12.7047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maestroni G. J. The immunoneuroendocrine role of melatonin. J Pineal Res. 1993 Jan;14(1):1–10. doi: 10.1111/j.1600-079x.1993.tb00478.x. [DOI] [PubMed] [Google Scholar]
- Moret Y., Schmid-Hempel P. Survival for immunity: the price of immune system activation for bumblebee workers. Science. 2000 Nov 10;290(5494):1166–1168. doi: 10.1126/science.290.5494.1166. [DOI] [PubMed] [Google Scholar]
- Nava F., Calapai G., Facciolà G., Cuzzocrea S., Giuliani G., De Sarro A., Caputi A. P. Melatonin effects on inhibition of thirst and fever induced by lipopolysaccharide in rat. Eur J Pharmacol. 1997 Jul 23;331(2-3):267–274. doi: 10.1016/s0014-2999(97)01049-2. [DOI] [PubMed] [Google Scholar]
- Nelson R. J., Blom J. M. Photoperiodic effects on tumor development and immune function. J Biol Rhythms. 1994 Winter;9(3-4):233–249. doi: 10.1177/074873049400900305. [DOI] [PubMed] [Google Scholar]
- Nelson R. J., Demas G. E. Role of melatonin in mediating seasonal energetic and immunologic adaptations. Brain Res Bull. 1997;44(4):423–430. doi: 10.1016/s0361-9230(97)00222-0. [DOI] [PubMed] [Google Scholar]
- Nelson R. J., Drazen D. L. Melatonin mediates seasonal adjustments in immune function. Reprod Nutr Dev. 1999 May-Jun;39(3):383–398. doi: 10.1051/rnd:19990310. [DOI] [PubMed] [Google Scholar]
- Netea M. G., Kullberg B. J., Van der Meer J. W. Circulating cytokines as mediators of fever. Clin Infect Dis. 2000 Oct;31 (Suppl 5):S178–S184. doi: 10.1086/317513. [DOI] [PubMed] [Google Scholar]
- Plata-Salamán C. R., Vasselli J. R., Sonti G. Differential responsiveness of obese (fa/fa) and lean (Fa/Fa) Zucker rats to cytokine-induced anorexia. Obes Res. 1997 Jan;5(1):36–42. doi: 10.1002/j.1550-8528.1997.tb00281.x. [DOI] [PubMed] [Google Scholar]
- Raghavendra V., Agrewala J. N., Kulkarni S. K. Melatonin reversal of lipopolysacharides-induced thermal and behavioral hyperalgesia in mice. Eur J Pharmacol. 2000 Apr 21;395(1):15–21. doi: 10.1016/s0014-2999(00)00196-5. [DOI] [PubMed] [Google Scholar]
- Rothwell N. J. Sixteenth Gaddum Memorial Lecture December 1996. Neuroimmune interactions: the role of cytokines. Br J Pharmacol. 1997 Jul;121(5):841–847. doi: 10.1038/sj.bjp.0701248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saper C. B. Neurobiological basis of fever. Ann N Y Acad Sci. 1998 Sep 29;856:90–94. doi: 10.1111/j.1749-6632.1998.tb08317.x. [DOI] [PubMed] [Google Scholar]
- Steinlechner S., Heldmaier G. Role of photoperiod and melatonin in seasonal acclimatization of the Djungarian hamster, Phodopus sungorus. Int J Biometeorol. 1982 Dec;26(4):329–337. doi: 10.1007/BF02219503. [DOI] [PubMed] [Google Scholar]
- Viteri F. E., Liu X., Tolomei K., Martín A. True absorption and retention of supplemental iron is more efficient when iron is administered every three days rather than daily to iron-normal and iron-deficient rats. J Nutr. 1995 Jan;125(1):82–91. doi: 10.1093/jn/125.1.82. [DOI] [PubMed] [Google Scholar]
- Wing E. J., Young J. B. Acute starvation protects mice against Listeria monocytogenes. Infect Immun. 1980 Jun;28(3):771–776. doi: 10.1128/iai.28.3.771-776.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright A. C., Simpson L. M., Oliver J. D. Role of iron in the pathogenesis of Vibrio vulnificus infections. Infect Immun. 1981 Nov;34(2):503–507. doi: 10.1128/iai.34.2.503-507.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Miert A. S., van Duin C. T., Schotman A. J., Franssen F. F. Clinical, haematological and blood biochemical changes in goats after experimental infection with tick-borne fever. Vet Parasitol. 1984 Nov;16(3-4):225–233. doi: 10.1016/0304-4017(84)90040-2. [DOI] [PubMed] [Google Scholar]