Abstract
Individuals of many species experience marked seasonal variation in environmental conditions and must adapt to potentially large fluctuations in energy availability and expenditure. Seasonal changes in immunity have likely evolved as an adaptive mechanism to cope with seasonal stressors. In addition, these changes may be constrained by seasonal fluctuations in energy availability. The goal of this study was to assess the role of energetic trade-offs associated with seasonal variation in immunity. In addition to body fat stores, metabolic fuels (e.g., glucose) may affect immune function in seasonally breeding rodents. In this study we experimentally reduced energy availability via injections of the metabolic inhibitor 2-deoxy-d-glucose (2-DG) in long- and short-day housed Siberian hamsters (Phodopus sungorus) and then examined antigen-specific antibody production. Metabolic stress decreased antibody response compared with control animals in long days. In contrast, no difference was observed between treatment groups in short days. These data suggest that reductions in energy availability suppress immunity and short days buffer organisms against glucoprivation-induced immunosuppression.
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Abbreviations
- 2-DG:
-
2-Deoxy-d-glucose
- IgM:
-
Immunoglobulin M
- IgG:
-
Immunoglobulin G
- KLH:
-
Keyhole limpet hemocyanin
- PWAT:
-
Parametrial white adipose tissue
- IWAT:
-
Inguinal white adipose tissue
- RWAT:
-
Retroperitoneal white adipose tissue
- ELISA:
-
Enzyme-linked immunosorbent assay
- EIA:
-
Enzyme immunoassay
- PBS-T:
-
Phosphate buffered saline with Tween-20
- OD:
-
Optical density
- ANOVA:
-
Analysis of variance
- PVN:
-
Paraventricular nucleus
- AVP:
-
Arginine vasopressin
- CRH:
-
Corticotropin-releasing hormone
References
Altizer S, Dobson A, Hosseini P, Hudson P, Pascual M, Rohani P (2006) Seasonality and the dynamics of infectious disease. Ecol Lett 9:467–484
Bartness TJ, Goldman BD (1989) Mammalian pineal melatonin: a clock for all seasons. Experientia 45:939–945
Bartness TJ, Wade GN (1985) Photoperiodic control of seasonal body weight cycles in hamsters. Neurosci Biobehav Rev 9:599–612
Bartness TJ, Powers JB, Hastings MH, Bittman EL, Goldman BD (1993) The timed infusion paradigm for melatonin delivery: what it has taught us about the melatonin signal, its reception, the photoperiodic control of seasonal responses. J Pineal Res 15:161–190
Bilbo SD, Nelson RJ (2003) Sex differences in photoperiodic and stress-induced enhancement of immune function in Siberian hamsters. Brain Behav Immun 17:462–472
Bilbo SD, Drazen DL, Quan N, He L, Nelson RJ (2002) Short day lengths attenuate the symptoms of infection in Siberian hamsters. Proc R Soc Lond B Biol Sci 269:447–454
Bronson FH (1989) Mammalian reproductive biology. University of Chicago Press, Chicago
Bronson FH, Heideman PD (1994) Seasonal regulation of reproduction in mammals. In: Knobil E, Neill JD (eds) The physiology of reproduction, 2nd edn. Raven, New York, pp 541–584
Caroleo MC, Frasca D, Nistico G, Doria G (1992) Melatonin as an immunomodulator in immunodeficient mice. Immunopharmacology 23:81–89
Cassone VM (1990) Melatonin: time in a bottle. Oxf Rev Reprod Biol 12:319–367
Dark J, Zucker I (1983) Short photoperiods reduce winter energy requirements of the Meadow vole (Microtus pennsylvanicus). Physiol Behav 31:699–702
Dark J, Miller DR, Zucker I (1994) Reduced glucose availability induces torpor in Siberian hamster. Am J Physiol 267:R496–R501
Demas GE (2004) The energetics of immunity: a neuroendocrine link between energy balance and immune function. Horm Behav 45:173–180
Demas GE, Nelson RJ (1996) The effects of photoperiod and temperature on immune function of adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 11:94–102
Demas GE, Nelson RJ (1998) Exogenous melatonin enhances cell-mediated, but not humoral, immune function in deer mice (Perimyscus maiculatus). J Comp Physiol A 179:819–825
Demas GE, DeVries AC, Nelson RJ (1997) Effects of photoperiod and 2-deoxy-d-glucose-induced metabolic stress on immune function in female deer mice. Am J Physiol 272:610–616
Demas GE, Drazen DL, Jasnow AM, Bartness TJ, Nelson RJ (2002) Sympathoadrenal system differentially affects photoperiodic changes in humoral immunity of Siberian hamsters (Phodopus sungorus). J Neuroendocrinol 14:29–35
Demas GE, Drazen DL, Nelson RJ (2003a) Reductions in total body fat decrease humoral immunity. Proc R Soc Lond B Biol Sci 270:905–911
Demas GE, Bartness TJ, Nelson RJ, Drazen DL (2003b) Photoperiod modulates the effects of norepinephrine on lymphocyte proliferation in Siberian hamsters. Am J Physiol 285:R873–R879
Demas GE, Johnson C, Polacek KM (2004) Social interactions differentially affect reproductive and immune responses of Siberian hamsters. Physiol Behav 83:73–79
Dhabhar FS (2000) Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking. Ann N Y Acad Sci 917:876–893
Dixon F, Jacot-Guillarmod H, McConahey PJ (1966) The antibody responses of rabbits and rats to hemocyanin. J Immunol 97:350–355
Dowell SF, Whitney CG, Rose CE, Schuchat A (2003) Seasonal patterns of invasive pneumococcal disease. Emerg Infect Dis 9:573–579
Drazen DL, Nelson RJ, Bartness TJ, Demas GE (2000) Sympathoadrenal regulation of photoperiodic changes in immune function in Siberian hamsters. Society for Neuroscience, New Orleans
Drazen DL, Demas GE, Nelson RJ (2001) Leptin effects on immune function and energy balance are photoperiod-dependent in Siberian hamsters (Phodopus sungorus). Endocrinology 142:2768–2775
Evans SB, Wilkinson CW, Bentson K, Gronbeck P, Zavosh A, Figlewicz DP (2001) PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat. Am J Physiol Regul Integr Comp Physiol 281:R1426–R1436
Goldman BD, Elliot RJ (1988) Photoperiodism and seasonality in hamsters: role of the pineal gland. In: Stetson MH (ed) Processing of environmental information in vertebrates. Springer, Berlin Heidelberg New York, pp 203–218
Goldman BD, Nelson RJ (1993) Melatonin and seasonality in mammals. In: Yu HS, Reiter RJ (eds) Melatonin: biosynthesis, physiological effects and clinical applications. CRC, New York
Gorman MR, Zucker I (1997) Environmental induction of photoresponsiveness in the Siberian hamster (Photopus sungorus). Am J Physiol Reg I 41:R887–R895
Heldmaier G, Steinlechner S, Ruf T, Wiesinger H, Klingenspor K (1989) Photoperiod and thermoregulation in vertebrates: body temperature rhythms and thermogenic acclimation. J Biol Rhythms 4:351–365
Henken AM, Brandsma HA (1982) The effects of environmental temperature on immune response and metabolism of the young chicken. Poult Sci 61:1667–1677
Hoffman K, Illnerova H, Vanecek J (1985) Comparison of pineal melatonin rhythms in young adult and old Djungarian hamsters (Phodopus sungorus) under long and short photoperiods. Neurosci Lett 56:39–43
Horton RW, Meldrum BS, Bachelard HS (1973) Enzymic and cerebral metabolic effects of 2-deoxy-d-glucose. J Neurochem 21:507–520
Hosseini PR, Dhondt AA, Dobson A (2004) Seasonal and wildlife disease: how seasonal birth, aggregation, and variation in immunity effect the dynamics of Mycoplasma gallisepticum in house finches. Proc R Soc Lond B Biol Sci 271:2569–2577
Iverson SL, Turner BN (1974) Winter weight dynamics in Microtus pennsylvanicus. Ecology 55:1030–1040
John JL (1994) The avian spleen: a neglected organ. Q Rev Biol 69:327–351
Kinsey SG, Prendergast BJ, Nelson RJ (2003) Photoperiod and stress affect wound healing in Siberian hamsters. Physiol Behav 78:205–211
Lochmiller RL, Deerenberg C (2000) Trade-offs in evolutionary immunology: just what is the cost of immunity? Oikos 88:87–98
Lochmiller RL, Vesty MR, McMurray ST (1994) Temporal variation in humoral and cell-mediated immune response in Sigmodon hispidus population. Ecology 75:236–245
Lynch GR, Lynch CB, Kliman RM (1989) Genetic analysis of photoresponsiveness in the Djungarian hamster, Phodopus sungorus. J Comp Physiol A 164:475–481
Lysle DT, Cunnick JE, Wu R, Caggiula AR, Wood PG, Rabin BS (1988) 2-Deoxy-d-glucose modulation of T-lymphocyte reactivity: differential effects on lymphoid compartments. Brain Behav Immun 2:212–221
Maestroni GJ (1993) The immunoendocrine role of melatonin. J Pineal Res 14:1–10
Margraff RR, Zlomanczuk P, Liskin LA, Lynch GR (1991) Circadian differences in neuronal activity of the suprachiasmatic nucleus in brain slices prepared from photo-responsive and photo-non-responsive Djungarian hamsters. Brain Res 544:42–48
Mann DR, Akinbami MA, Gould KG, Ansari AA (2000) Seasonal variations in cytokine expression and cell-mediated immunity in male rhesus monkeys. Cell Immunol 200:105–115
Moffatt CA, DeVries AC, Nelson RJ (1993) Winter adaptations of male deer mice and prairie voles that vary in reproductive responsiveness to photoperiod. J Biol Rhythms 8:221–232
Motawei K, Pyner S, Ranson RN, Kamel M, Coote JH (1999) Terminals of paraventricular spinal neurons are closely associated with adrenal medullary sympathetic preganglion neurons: immunocytochemical evidence for vasopressin as a possible neurotransmitter in this pathway. Exp Brain Res 126:68–76
Nelson RJ, Demas GE (1996) Seasonal changes in immune function. Q Rev Biol 71:511–48
Nelson RJ, Badura LL, Goldman BD (1990) Mechanisms of seasonal cycles of behavior. Ann Rev Psychol 41:81–109
Prendergast BJ, Kreigsfeld LJ, Nelson RJ (2001) Photoperiodic polyphenisms in rodents: neuroendocrine mechanisms, costs, and functions. Q Rev Biol 76:293–325
Prendergast BJ, Wynne-Edwards KE, Yellon SM, Nelson RJ (2002) Photorefractoriness of immune function in male Siberian hamsters (Phodopus sungorus). J Neuroendocrinol 14:318–329
Puchalski W, Lynch RG (1986) Evidence for differences in the circadian organization of hamsters exposed to short day photoperiod. J Comp Physiol A 159:7–11
Puchalski W, Lynch RG (1988) Daily melatonin injections affect the expression of circadian rhythmicity in Djungarian hamsters kept under a long-day photoperiod. Neuroendocrinology 48:280–286
Reburn CJ, Wynne-Edwards KE (1999) Cortisol and prolactin concentrations during repeated blood sample collection from freely moving, mouse-sized animals (Phodopus spp.). Comp Med 50:184–198
Ribelayga C, Pevet P, Simonneaux V (2000) HIOMT drives photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster. Am J Physiol Reg I 278:R1339–R1345
Ruby NF, Zucker I (1992) Daily torpor in the absence of the superchiasmatic nucleus in the Siberian hamster. Am J Physiol A 263:R353–R362
Sheldon BC, Verhulst S (1996) Ecological immunology: costly parasite defenses and trade-offs in evolutionary psychology. Trends Ecol Evol 11:317–321
Weindenfeld J, Corcos AP, Wohlman A, Feldman S (1994) Characterization of the 2-deoxyglucose effect on the adrenocortical axis. Endocrinology 134:1924–1931
Yates FE, Russell SM, Dallman MF, Hodge GA, McCann SM, Dhariwal AP (1971) Potentiation by vasopressin of corticotropin release induced by corticotropin-releasing factor. Endocrinology 88:3–15
Yellon SM, Teasly LA, Fagoagal OR, Nguyen HC, Truong HN, Cannerella L (1999) Role of photoperiod and the pineal gland in T-cell dependent humoral immune reactivity in the Siberian hamster. J Pineal Res 29:86–93
Acknowledgments
We thank Melissa-Ann L. Scotti, Timothy J. Greives, Andrew Garst, and Emily Chester for their assistance and two anonymous reviewers for helpful suggestions on this manuscript. This work was supported in part by NIH T32 Training Grant HD049336, a Faculty Research Support Program Grant, and the Center for the Integrative Study of Animal Behavior (CISAB). All procedures were approved by the Bloomington Institutional Animal Care and Use Committee.
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Communicated by G. Heldmaier.
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Zysling, D.A., Demas, G.E. Metabolic stress suppresses humoral immune function in long-day, but not short-day, Siberian hamsters (Phodopus sungorus). J Comp Physiol B 177, 339–347 (2007). https://doi.org/10.1007/s00360-006-0133-4
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DOI: https://doi.org/10.1007/s00360-006-0133-4