Abstract
Short days inhibit reproduction and enhance immune function in deer mice (Peromyscus maniculatus). Their reproductive inhibition is sustained by an endogenous timing mechanism: after ca. 20 weeks in short days, reproductive photorefractoriness develops, followed by spontaneous recrudescence of the reproductive system. It is unknown whether analogous seasonal timing mechanisms regulate their immune function or whether enhanced immune function is sustained indefinitely under short days. In order to test this hypothesis, we housed adult male deer mice under long (16 h light day(-1)) or short (8 h light day(-1)) day conditions for 32 weeks or under long day conditions for 20 weeks followed by 12 weeks of short days. Mice under the long day conditions remained photostimulated over the 32 weeks, whereas mice housed under the short day conditions exhibited gonadal regression followed by photorefractoriness and spontaneous recrudescence. Mice transferred to short days at week 20 were reproductively photoregressed at week 32. Total splenocytes, relative splenic mass and mitogen-activated splenocyte proliferation were greater in those mice transferred to short days at week 20 than in those mice housed under either long or short day conditions for 32 consecutive weeks, and immune function in mice exposed to short days for 32 weeks was comparable with that of long day animals. These data suggest that short day enhancement of immune function is not indefinite. With prolonged (< or = 32 weeks) exposure to short days, several measures of immune function exhibit "spontaneous" regression, restoring long day-like immunocompetence. The results suggest that formal similarities and, possibly, common substrates exist among the photoperiodic timekeeping mechanisms that regulate seasonal transitions in reproductive and immune function.
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- Azcona-Olivera J. I., Ouyang Y. L., Warner R. L., Linz J. E., Pestka J. J. Effects of vomitoxin (deoxynivalenol) and cycloheximide on IL-2, 4, 5 and 6 secretion and mRNA levels in murine CD4+ cells. Food Chem Toxicol. 1995 Jun;33(6):433–441. doi: 10.1016/0278-6915(95)00012-q. [DOI] [PubMed] [Google Scholar]
- Bertoni J. M., Sprenkle P. M., Hanifin J. P., Stetson M. H., Brainard G. C. Effects of short photoperiod on ATPase activities in the testis of the immature Siberian hamster. Biol Reprod. 1992 Oct;47(4):509–513. doi: 10.1095/biolreprod47.4.509. [DOI] [PubMed] [Google Scholar]
- Bittman E. L. Hamster refractoriness: the role of insensitivity of pineal target tissues. Science. 1978 Nov 10;202(4368):648–650. doi: 10.1126/science.568311. [DOI] [PubMed] [Google Scholar]
- Blank J. L., Desjardins C. Photic cues induce multiple neuroendocrine adjustments in testicular function. Am J Physiol. 1986 Feb;250(2 Pt 2):R199–R206. doi: 10.1152/ajpregu.1986.250.2.R199. [DOI] [PubMed] [Google Scholar]
- Blom J. M., Gerber J. M., Nelson R. J. Day length affects immune cell numbers in deer mice: interactions with age, sex, and prenatal photoperiod. Am J Physiol. 1994 Aug;267(2 Pt 2):R596–R601. doi: 10.1152/ajpregu.1994.267.2.R596. [DOI] [PubMed] [Google Scholar]
- Brainard G. C., Knobler R. L., Podolin P. L., Lavasa M., Lublin F. D. Neuroimmunology: modulation of the hamster immune system by photoperiod. Life Sci. 1987 Mar 30;40(13):1319–1326. doi: 10.1016/0024-3205(87)90589-3. [DOI] [PubMed] [Google Scholar]
- Brainard G. C., Watson-Whitmeyer M., Knobler R. L., Lublin F. D. Neuroendocrine regulation of immune parameters. Photoperiod control of the spleen in Syrian hamsters. Ann N Y Acad Sci. 1988;540:704–706. doi: 10.1111/j.1749-6632.1988.tb27219.x. [DOI] [PubMed] [Google Scholar]
- Cogoli A. The effect of hypogravity and hypergravity on cells of the immune system. J Leukoc Biol. 1993 Sep;54(3):259–268. doi: 10.1002/jlb.54.3.259. [DOI] [PubMed] [Google Scholar]
- Cory A. H., Owen T. C., Barltrop J. A., Cory J. G. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 1991 Jul;3(7):207–212. doi: 10.3727/095535491820873191. [DOI] [PubMed] [Google Scholar]
- Demas G. E., Klein S. L., Nelson R. J. Reproductive and immune responses to photoperiod and melatonin are linked in Peromyscus subspecies. J Comp Physiol A. 1996 Dec;179(6):819–825. doi: 10.1007/BF00207360. [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]
- Demas G. E., Nelson R. J. Photoperiod and temperature interact to affect immune parameters in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms. 1996 Jun;11(2):94–102. doi: 10.1177/074873049601100202. [DOI] [PubMed] [Google Scholar]
- Di Stefano A., Paulesu L. Inhibitory effect of melatonin on production of IFN gamma or TNF alpha in peripheral blood mononuclear cells of some blood donors. J Pineal Res. 1994 Nov;17(4):164–169. doi: 10.1111/j.1600-079x.1994.tb00128.x. [DOI] [PubMed] [Google Scholar]
- Freeman D. A., Zucker I. Refractoriness to melatonin occurs independently at multiple brain sites in Siberian hamsters. Proc Natl Acad Sci U S A. 2001 May 15;98(11):6447–6452. doi: 10.1073/pnas.111140398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gieni R. S., Li Y., HayGlass K. T. Comparison of [3H]thymidine incorporation with MTT- and MTS-based bioassays for human and murine IL-2 and IL-4 analysis. Tetrazolium assays provide markedly enhanced sensitivity. J Immunol Methods. 1995 Nov 16;187(1):85–93. doi: 10.1016/0022-1759(95)00170-f. [DOI] [PubMed] [Google Scholar]
- Goldman B. D. Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms of photoperiodic time measurement. J Biol Rhythms. 2001 Aug;16(4):283–301. doi: 10.1177/074873001129001980. [DOI] [PubMed] [Google Scholar]
- Gorman M. R., Zucker I. Seasonal adaptations of Siberian hamsters. II. Pattern of change in daylength controls annual testicular and body weight rhythms. Biol Reprod. 1995 Jul;53(1):116–125. doi: 10.1095/biolreprod53.1.116. [DOI] [PubMed] [Google Scholar]
- Gorman M. R., Zucker I. Testicular regression and recrudescence without subsequent photorefractoriness in Siberian hamsters. Am J Physiol. 1995 Oct;269(4 Pt 2):R800–R806. doi: 10.1152/ajpregu.1995.269.4.R800. [DOI] [PubMed] [Google Scholar]
- Heath H. W., Lynch G. R. Effects of 18 weeks of daily melatonin injection on reproduction and temperature regulation in the mouse, Peromyscus leucopus. J Exp Zool. 1981 Apr;216(1):193–195. doi: 10.1002/jez.1402160122. [DOI] [PubMed] [Google Scholar]
- Herbert T. B., Cohen S. Stress and immunity in humans: a meta-analytic review. Psychosom Med. 1993 Jul-Aug;55(4):364–379. doi: 10.1097/00006842-199307000-00004. [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]
- Kitamura T., Tange T., Terasawa T., Chiba S., Kuwaki T., Miyagawa K., Piao Y. F., Miyazono K., Urabe A., Takaku F. Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J Cell Physiol. 1989 Aug;140(2):323–334. doi: 10.1002/jcp.1041400219. [DOI] [PubMed] [Google Scholar]
- Klemcke H. G., Bartke A., Goldman B. D. Plasma prolactin concentrations and testicular human chorionic gonadotropin binding sites during short photoperiod-induced testicular regression and recrudescence in the golden hamster. Biol Reprod. 1981 Oct;25(3):536–548. doi: 10.1095/biolreprod25.3.536. [DOI] [PubMed] [Google Scholar]
- Lincoln G. A., Richardson M. Photo-neuroendocrine control of seasonal cycles in body weight, pelage growth and reproduction: lessons from the HPD sheep model. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Jun;119(3):283–294. doi: 10.1016/s0742-8413(98)00017-6. [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., Klein S. L., Kriegsfeld L. J. The influence of season, photoperiod, and pineal melatonin on immune function. J Pineal Res. 1995 Nov;19(4):149–165. doi: 10.1111/j.1600-079X.1995.tb00184.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson R. J., Demas G. E. Seasonal changes in immune function. Q Rev Biol. 1996 Dec;71(4):511–548. doi: 10.1086/419555. [DOI] [PubMed] [Google Scholar]
- Palacios R. Mechanism of T cell activation: role and functional relationship of HLA-DR antigens and interleukins. Immunol Rev. 1982;63:73–110. doi: 10.1111/j.1600-065x.1982.tb00412.x. [DOI] [PubMed] [Google Scholar]
- Prendergast B. J., Yellon S. M., Tran L. T., Nelson R. J. Photoperiod modulates the inhibitory effect of in vitro melatonin on lymphocyte proliferation in female Siberian hamsters. J Biol Rhythms. 2001 Jun;16(3):224–233. doi: 10.1177/074873040101600305. [DOI] [PubMed] [Google Scholar]
- Simpson S. M., Follett B. K., Ellis D. H. Modulation by photoperiod of gonadotrophin secretion in intact and castrated Djungarian hamsters. J Reprod Fertil. 1982 Sep;66(1):243–250. doi: 10.1530/jrf.0.0660243. [DOI] [PubMed] [Google Scholar]
- Yellon S. M., Fagoaga O. R., Nehlsen-Cannarella S. L. Influence of photoperiod on immune cell functions in the male Siberian hamster. Am J Physiol. 1999 Jan;276(1 Pt 2):R97–R102. doi: 10.1152/ajpregu.1999.276.1.R97. [DOI] [PubMed] [Google Scholar]