Melatonin and immune function: Hype or hypothesis?

Critical Reviews in Immunology

Volumn 22, Issue 5-6, 2002, Pages 351-371

  Hotchkiss, Andrew K ^a   Nelson, Randy J ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

Energetic cost; Photoperiodism; Pineal; Seasonal rhythms

Indexed keywords

ANTIBODY; CONCANAVALIN A; CYTOKINE; HEMAGGLUTININ; IMMUNOGLOBULIN E; IMMUNOGLOBULIN M; LIPOPOLYSACCHARIDE; MELATONIN; MITOGENIC AGENT; SEROTONIN;

ANTIBODY PRODUCTION; CELLULAR IMMUNITY; ENERGY TRANSFER; HUMAN; HUMORAL IMMUNITY; IMMUNE FUNCTION TEST; IMMUNE RESPONSE; IMMUNOMODULATION; LYMPHOCYTE PROLIFERATION; LYMPHOID TISSUE; NONHUMAN; PHAGOCYTOSIS; PHOTOPERIODICITY; PINEAL BODY; PRIORITY JOURNAL; REPRODUCTION; REVIEW; SEASONAL VARIATION; SURVIVAL; TUMOR IMMUNITY; WINTER;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; HUMANS; IMMUNE SYSTEM; MELATONIN; PHOTOPERIOD; SEASONS;

EID: 0038669232     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (180)

1. Goldman BD, Nelson RJ. Melatonin and seasonality in mammals. In: Yu HS, Reiter RJ, editors. Melatonin: Biosynthesis, Physiological Effects and Clinical Applications. Boca Raton, FL: CRC Press, 1993: 225-252.
2. Moffatt CA, DeVries AC, Nelson RJ. Winter adaptations of male deer mice (Peromyscus maniculatus) and prairie voles (Microtus ochrogaster) that vary in reproductive responsiveness to photoperiod. J Biol Rhythms 1993; 8(3):221-232.
3. Bronson FH, Heideman PN. Seasonal regulation of reproduction in mammals. In: Knobil E, Neil JD, editors. The Physiology of Reproduction. New York: Raven Press, 1994: 541-584.
4. Bronson FH. Mammalian Reproductive Biology. Chicago: University of Chicago Press, 1989.
5. Nelson RJ, Demas GE. Role of melatonin in mediating seasonal energetic and immunologic adaptations. Brain Res Bull 1997; 44(4):423-430.
6. Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ. The influence of season, photoperiod, and pineal melatonin on immune function. J Pineal Res 1995; 19(4):149-165.
7. Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ. Seasonal Patterns of Stress, Immune Function, and Disease. Cambridge: Cambridge University Press, 2002.
8. Lopez-Gonzalez MA, Martin-Cacao A, Calvo JR, Reiter RJ, Osuna C, Guerrero JM. Specific binding of 2-[125I]melatonin by partially purified membranes of rat thymus. J Neuroimmunol 1993; 45(1-2):121-126.
9. McShae WJ. Social tolerance and proximate mechanisms of dispersal among winter groups of meadow voles (Microtus pennsylvanicus). Anim Behav 1990; 39:346-351.
10. Goldman BD. Mammalian photoperiodic system: Formal properties and neuroendocrine mechanisms of photoperiodic time measurement. J Biol Rhythms 2001; 16:283-301.
11. Heldmaier G, Steinlechner S, Ruf T, Wiesinger H, Klingenspor M. Photoperiod and thermoregulation in vertebrates: Body temperature rhythms and thermogenic acclimation. J Biol Rhythms 1989; 4:251-265.
12. Prendergast BJ, Kriegsfeld LJ, Nelson RJ. Photoperiodic polyphenisms in rodents: neuroendocrine mechanisms, costs, and functions. Q Rev Biol 2001; 76(3):293-325.
13. Kelley KW. Immunological consequences of changing environmental stimuli. In: Moberg GP, editor. Animal Stress. Bethesda, MD: American Physiological Society, 1985: 193-223.
14. Demas GE, Chefer V, Talan MI, Nelson RJ. Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice. Am J Physiol 1997; 273(5 Pt 2):R1631-1637.
15. Moret Y, Scmid-Hempel P. Survival for immunity: The price of immune system activation for bumblebee workers. Science 2000; 290:1166-1168.
16. Henken AM, Brandsma HA. The effect of environmental temperature on immune response and metabolism of the young chicken. 2. Effect of the immune response to sheep red blood cells on energy metabolism. Poult Sci 1982; 61(8):1667-1673.
17. Lochmiller RL, Vesty MR, McMurry ST. Temporal variation in humoral and cell-mediated immune response in a Sigmodon hispidus population. Ecology 1994; 75:236-245.
18. John JL. The avian spleen: A neglected organ. Q Rev Biol 1994; 69:327-351.
19. Nelson RJ, Demas GE. Seasonal changes in immune function. Q Rev Biol 1996; 71(4):511-548.
20. Ader R, Cohen N. Psychoneuroimmunology: conditioning and stress. Annu Rev Psychol 1993; 44:53-85.
21. Berczi I. The influence of the pituitary-adrenal axis on the immune system. In: Berczi I, editor. Pituitary Function and Immunity. Boca Raton: CRC Press, 1986.
22. Black PH. Central nervous system-immune system interactions: psychoneuroendocrinology of stress and its immune consequences. Antimicrob Agents Chemother 1994; 38(1):1-6.
23. Newson J. Seasonal differences in reticulocyte count, hemoglobin levels, and spleen weight in wild voles. Br J Haematol 1962; 8:296-302.
24. Valentine GL, Kirkpatrick RL. Seasonal changes in reproductive and related organs in the pine vole, Microtus pinetorum, in southwestern Virginia. J Mammal 1970; 51:553-560.
25. Sealander JA, Bickerstaff LK. Seasonal changes in reticulocyte number and in relative weights of the spleen, thymus, and kidneys in the northern redbacked mouse. Can J Zool 1967; 45(3):253-260.
26. MacMurray JP, Barker JP, Armstrong JD, Bozzetti LP, Kuhn IN. Circannual changes in immune function. Life Sci 1983; 32(20):2363-2370.
27. Bratescu A, Teodorescu M. Circannual variations in the B cell/T cell ratio in normal human peripheral blood. J Allergy Clin Immunol 1981 68(4):273-280.
28. Komada H, Nakabayashi N, Yoahida T, Takanari H, Hara M, Takahashi T, Izutsu K. Seasonal variation in mitogenic response and subsets of human tonsillar lympocytes. J Interdiscipl Cycle Res 1989; 20:107-122.
29. Lyngbye J, Kroll J. Quantitative immunoelectrophoresis of proteins in serum from a normal population: season-, age-, and sex-related variations. Clin Chem 1971; 17(6):495-500.
30. Stoop JW, Zegers BJ, Sander PC, Ballieux RE. Serum immunoglobulin levels in healthy children and adults. Clin Exp Immunol 1969; 4(1):101-112.
31. Nordby GL, Cassidy JT. Seasonal effect on the variability of summer immunoglobulin levels. Hum Biol 1983; 55(4):797-809.
32. Mason BH, Holdaway IM, Stewart AW, Neave LM, Kay RG. Season of initial discovery of tumour as an independent variable predicting survival in breast cancer. Br J Cancer 1991; 63(1):157.
33. McWhirter WR, Dobson C. Childhood melanoma in Australia. World J Surg 1995; 19(3):334-336.
34. Garner WW, Allard HA. Photoperiodism, the response of the plant to relative length of day and night. Science 1922; 60:582-583.
35. Prendergast BJ, Nelson RJ, Zucker I. Mammalian seasonal rhythms: Behavior and neuroendocrine substrates. In: Pfaff DW, editor. Hormones, Brain, and Behavior, Vol 2. San Diego, CA: Academic Press, 2002: 93-156.
36. Reiter RJ. The Pineal and Its Hormones. New York: Alan R Liss, 1982.
37. Eakin RM. The Third Eye. Berkeley: University of California Press, 1973.
38. Hansen JT, Karasek M. Neuron or endocrine cell? The pinealocyte as a paraneuron. Prog Clin Biol Res 1982; 92:1-9.
39. Cassone VM. Effects of melatonin on vertebrate circadian systems. Trends Neurosci 1990; 13(11):457-464.
40. Bartness TJ, Powers JB, Hastings MH, Bittman EL, Goldman BD. 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; 15:161-190.
41. Bittman EL, Karsch FJ. Nightly duration of pineal melatonin secretion determines the reproductive response to inhibitory day length in ewe. Biol Reprod 1984; 30:585-593.
42. Carter DS, Goldman BD. Antigonadal effects of timed melatonin infusion in pinealectomized male Djungarian hamsters (Phodopus sungorus sungorus): Mediation by melatonin. Endocrinology 1983; 113:1261-1267.
43. Reiter RJ. The melatonin rhythm: both a clock and a calendar. Experientia 1993; 49(8):654-664.
44. Reppert SM, Weaver DR, Godson C. Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol Sci 1996 17(3):100-102.
45. Reppert SM. Melatonin receptors: molecular biology of a new family of G protein-coupled receptors. J Biol Rhythms 1997; 12(6):528-531.
46. Drazen DL, Bilu D, Bilbo SD, Nelson RJ. Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist. Am J Physiol Regul Integr Comp Physiol 2001 280(5): R1476-1482.
47. Drazen DL, Nelson RJ. Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity. Neuroendocrinology 2001; 74(3):178-184.
48. Smirnov AN. Nuclear melatonin receptors. Biochemistry (Mosc) 2001; 66(1):19-26.
49. Skwarlo-Sonta K. Melatonin in immunity: comparative aspects. Neuroendocrinol Lett 2002; 23 Suppl 1:61-66.
50. Rafii-el-Idrissi M, Calvo JR, Pozo D, Harmouch A, Guerrero JM. Specific binding of 2-[125I]iodomelatonin by rat splenocytes: characterization and its role on regulation of cyclic AMP production. J Neuroimmunol 1995; 57(1-2):171-178.
51. Martin-Cacao A, Lopez-Gonzalez MA, Reiter RJ, Calvo JR, Guerrero JM. Binding of 2-[125I]melatonin by rat thymus membranes during postnatal development. Immunol Lett 1993; 36(1):59-63.
52. Pang CS, Pang SF. High affinity specific binding of 2[125I]iodomelatonin by spleen membrane preparations of the chicken. J Pineal Res 1992; 12:167-173.
53. Poon AM, Pang SF. 2[125I]iodomelatonin binding sites in spleens of guinea pigs. Life Sci 1992; 50:1719-1726.
54. Sheldon BC, Verhulst S. Ecological immunology: costly parasite defenses and trade-offs in evolutionary ecology. TREE 1996; 11:317-321.
55. Maier SF, Watkins LR, Fleshner M. Psychoneuro-immunology. The interface between behavior, brain, and immunity. Am Psychol 1994; 49(12):1004-1017.
56. Lochmiller RL, Deerenberg C. Trade-offs in evolutionary immunology: just what is the cost of immunity? Oikos 2000; 88:87-98.
57. Kreymann G, Grosser S, Buggisch P, Gottschall C, Matthaei S, Greten H. Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock. Crit Care Med 1993; 21(7):1012-1019.
58. Chandra RK. Nutrition, immunity and infection: from basic knowledge of dietary manipulation of immune responses to practical application of ameliorating suffering and improving survival. Proc Natl Acad Sci USA 1996; 93:14304-14307.
59. Zuk M. Reproductive strategies and sex differences in disease susceptibility: An evolutionary viewpoint. Parasitol Today 1990; 6:231-233.
60. Zuk M, Johnsen TS. Seasonal changes in the relationship between ornamentation and immune response in red jungle fowl. Proc R Soc Lond B 1998; 265:205-210.
61. Merino S, Moller AP, de Lope F. Seasonal changes in cell-mediated immunocompetence and mass gain in nestling barn swallows: A parasite mediated effect? Oikos 2000; 90:327-332.
62. Afoke AO, Eeg-Olofsson O, Hed J, Hjellman N-I M, Lindblom B, Ludvigsson J. Seasonal variation and sex differences of circulating macrophages, immunoglobulins and lymphocytes in healthy school children. Scand J Immunol 1993; 7:209-215.
63. Boctor FN, Charmy RA, Cooper EL. Seasonal differences in the rhythmicity of human male and female lymphocyte blastogenic responses. Immunol Invest 1989; 18:775-784.
64. Sinclair JA, Lochmiller RL. The winter immuno-enhancement hypothesis: associations among immunity, density, and survival in prairie vole (Microtus ochrogaster) populations. Can J Zool 2000; 78:254.
65. Shivatcheva TM, Hadjioloff AI. Seasonal involution of gut-associated lymphoid tissue of the European ground squirrel. Dev Comp Immunol 1987a; 11:791-799.
66. Shivatcheva TM, Hadjioloff AI. Seasonal involution of the splenic lymphoid tissue of the European ground squirrel. Arkhiv Anaomii, Gistologii, I Embriologii 1987b; 92:48-53.
67. Stone WH. The J substance of cattle. III. Seasonal variation of the naturally occurring isoantibodies for the J substance. J Immunol 1956; 77:369-376.
68. Dobrowolska A, Rewkiwwicz-Dziarska A, Szarska I, Gill J. Seasonal changes in haematological parameters, levels of serum proteins and glycoproteins, activity of the thyroid gland, seprarenals and kidney in the common vole (Mircrotus arvalis Pall). J Interdiscipl Cycle Res 1974; 5:347-354.
69. Dobrowolska A, Adamczewska-Andrzejewska KA. Seasonal and long-term changes in serum gamma globulin levels in comparing the physiology and population density of the common vole, Microtus arvallis Pall. J Interdisc Cycle Res 1991; 22:1-19.
70. Sidky YA, Haywward J, Ruth RF. Seasonal variations of the immune response of ground squirrels kept at 22-24C. Can J Physiol Pharmacol 1972; 50:203-206.
71. Davis RL, Lochmiller RL. Quantitative and qualitative numerical alterations in splenocyte subpopulations of the cotton rat (Sigmodon hispidus) across seasons. Biol Rhythms Res 1995; 26:20-31.
72. Ratajczak HV, Thomas PT, Sothern RB, Vollmuth T, Heck JD. Evidence for genetic basis of seasonal differences in antibody formation between two mouse strains. Chronobiol Int 1993; 10:383-394.
73. Dozier MM, Ratajzzak HV, Sothern RB, Thomas PT. The influence of vehicle gavage on seasonality of the immune system parameters in the B6C3F1 mouse. Fundam Appl Toxicol 1997; 38:116-122.
74. Mann DR, Akinbami MA, Lunn SF. Endocrine-immune interaction: Alterations in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates. Am J Reprod Immunol 2000; 44:30-40.
75. Mann DR, Akinbami MA, Gould KG, Ansari AA. Seasonal variations in cytokine expression and cell-mediated immunity in male rhesus monkeys. Cell Immunol 2000; 200:105-115.
76. Melnikov OF, Nikolsky IS, Dugovaskaya LA, Valitskaya NA, Krabvchuk GP. Seasonal aspects of immunological reactivity of the human and animal organism. J Hyg Microbiol Immunol 1987; 31:225-230.
77. Giordano M, Vermeulen M, Palermo MS. Seasonal variations in antibody-dependent cellular cytotoxicity regulation by melatonin. FASEB J 1993; 7:1052-1054.
78. Planelles D, Hernandez-Godoy J, Montoro A, Montoro J, Gonzalez-Molina A. Seasonal variation in proliferative response and subpopulations of lymphocytes from mice housed in a constant environment. Cell Prolif 1994; 27(6):333-341.
79. Pati AK, Florentin I, Chung V, De Sousa M, Levi F, Mathe G. Circannual rhythm in natural killer activity and mitogen responsiveness of murine splenocytes. Cell Immunol 1987; 108(1):227-234.
80. Demas GE, Nelson RJ. Photoperiod and temperature interact to affect immune parameters in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 1996; 11(2):94-102.
81. Demas GE, Nelson RJ. Photoperiod, ambient temperature, and food availability interact to affect reproductive and immune function in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 1998; 13(3):253-262.
82. Demas GE, Nelson RJ. Short-day enhancement of immune function is independent of steroid hormones in deer mice (Peromyscus maniculatus). J Comp Physiol [B] 1998; 168(6):419-426.
83. Yellon SM, Fagoaga OR, Nehlsen-Cannarella SL. Influence of photoperiod on immune cell functions in the male Siberian hamster. Am J Physiol 1999; 276(1 Pt 2):R97-R102.
84. Prendergast BJ, Yellon SM, Tran LT, Nelson RJ. Photoperiod modulates the inhibitory effect of in vitro melatonin on lymphocyte proliferation in female Siberian hamsters. J Biol Rhythms 2001; 16(3):224-233.
85. Kluger MJ. Temperature regulation, fever, and disease. Int Rev Physiol 1979; 20:209-251.
86. Lochmiller RL, Vestey MR, McMurry ST. Selected immune responses of adult cotton rats (Sigmodon hispidus) to dietary restriction. Comp Biochem Physiol Comp Physiol 1993; 104(3):593-599.
87. Dhabhar FS, McEwen BS. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking. Brain Behav Immun 1997; 11(4):286-306.
88. Bilbo SD, Dhabhar FS, Viswanathan K, Saul A, Yellon SM, Nelson RJ. Short day lengths augment stress-induced leukocyte trafficking and stress-induced enhancement of skin immune function. Proc Natl Acad Sci USA 2002; 99(6):4067-4072.
89. Nelson RJ, Drazen DL. Melatonin mediates seasonal adjustments in immune function. Reprod Nutr Dev 1999; 39(3):383-398.
90. Caroleo MC, Frasca D, Nistico G, Doria G. Melatonin as immunomodulator in immunodeficient mice. Immunopharmacology 1992; 23(2):81-89.
91. Caroleo MC, Nistico G, Doria G. Effect of melatonin on the immune system. Pharmacol Res 1992; 26 Suppl 2:34-37.
92. Guerrero JM, Reiter RJ. A brief survey of pineal gland-immune system interrelationships. Endocr Res 1992; 18(2):91-113.
93. Pioli C, Caroleo MC, Nistico G, Doria G. Melatonin increases antigen presentation and amplifies specific and non specific signals for T-cell proliferation. Int J Immunopharmacol 1993; 15(4):463-468.
94. Poon AM, Liu ZM, Pang CS, Brown GM, Pang SF. Evidence for a direct action of melatonin on the immune system. Biol Signals 1994; 3(2):107-117.
95. Klein SL. Hormones and mating system affect sex and species differences in immune function among vertebrates. Behav Processes 2000; 51(1-3):149-166.
96. Klein SL. The effects of hormones on sex differences in infection: from genes to behavior. Neurosci Biobehav Rev 2000; 24(6):627-638.
97. Grossman CJ. Regulation of the immune system by sex steroids. Endocr Rev 1984; 5(3):435-455.
98. Konstadoulakis MM, Syrigos KN, Baxevanis CN, Syrigou EI, Papamichail M, Peveretos P, Anapliotou M, Golematis BC. Effect of testosterone administration, pre- and postnatally, on the immune system of rats. Horm Metab Res 1995; 27(6):275-278.
99. McCruden AB, Stimson WH. Androgen binding cytosol receptors in the rat thymus: physicochemical properties, specificity and localization. Thymus 1981; 3(2):105-117.
100. Grossman CJ. Interactions between the gonadal steroids and the immune system. Science 1985; 227(4684):257-261.
101. Drazen DL, Klein SL, Yellon SM, Nelson RJ. In vitro melatonin treatment enhances splenocyte proliferation in prairie voles. J Pineal Res 2000; 28(1):34-40.
102. Kriegsfeld LJ, Drazen DL, Nelson RJ. In vitro melatonin treatment enhances cell-mediated immune function in male prairie voles (Microtus ochrogaster). J Pineal Res 2001; 30(4):193-198.
103. Baxter JD, Forsham PH. Tissue effects of glucocorticoids. Am J Med 1972; 53(5):573-589.
104. Levi FA, Canon C, Touitou Y, Sulon J, Mechkouri M, Ponsart ED, Touboul JP, Vannetzel JM, Mowzowicz I, Reinberg A. Circadian rhythms in circulating T lymphocyte subtypes and plasma testosterone, total and free cortisol in five healthy men. Clin Exp Immunol 1988; 71(2):329-335.
105. Bhatnagar S, Mitchell JB, Betito K, Boksa P, Meaney MJ. Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning. Physiol Behav 1995; 57(4):633-639.
106. Murphy HM, Wideman CH. Vasopressin, corticosterone levels, and gastric ulcers during food-restriction stress. Peptides 1992; 13(2):373-376.
107. Persengiev S, Patchev V, Velev B. Melatonin effects on thymus steroid receptors in the course of primary antibody responses: significance of circulating glucocorticoid levels. Int J Biochem 1991; 23(12):1487-1489.
108. Aoyama H, Mori N, Mori W. Anti-glucocorticoid effects of melatonin on adult rats. Acta Pathol Jpn 1987; 37(7):1143-1148.
109. Aoyama H, Mori W, Mori N. Anti-glucocorticoid effects of melatonin in young rats. Acta Pathol Jpn 1986; 36(3):423-428.
110. Maestroni GJ, Conti A, Pierpaoli W. Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 1986; 13(1):19-30.
111. Matera L, Cesano A, Bellone G, Oberholtzer E. Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes. Brain Behav Immun 1992; 6(4):409-417.
112. Chen Y, Johnson AG. In vivo activation of macrophages by prolactin from young and aging mice. Int J Immunopharmacol 1993; 15(1):39-45.
113. Nelson RJ, Moffatt CA, Goldman BD. Reproductive and nonreproductive responsiveness to photoperiod in laboratory rats. J Pineal Res 1994; 17(3):123-131.
114. Vivien-Roels B, Malan A, Rettori MC, Delagrange P, Jeanniot JP, Pevet P. Daily variations in pineal melatonin concentrations in inbred and outbred mice. J Biol Rhythms 1998; 13(5):403-409.
115. Weaver DR, Liu C, Reppert SM. Nature's knockout: the Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters. Mol Endocrinol 1996; 10(11):1478-1487.
116. Csaba G, Barath P. Morphological changes of thymus and the thyroid gland after postnatal extirpation of pineal body. Endocrinol Exp 1975; 9(1):59-67.
117. Maestroni GJ, Conti A, Pierpaoli W. The pineal gland and the circadian, opiatergic, immunoregulatory role of melatonin. Ann N Y Acad Sci 1987; 496:67-77.
118. Haldar C, Singh R. Pineal modulation of thymus and immune function in a seasonally breeding tropical rodent, Funambulus pennanti. J Exp Zool 2001; 289(2):90-98.
119. Vaughan MK, Hubbard GB, Champney TH, Vaughan GM, Little JC, Reiter RJ. Splenic hypertrophy and extramedullary hematopoiesis induced in male Syrian hamsters by short photoperiod or melatonin injections and reversed by melatonin pellets or pinealectomy. Am J Anat 1987; 179(2):131-136.
120. Champney TH, McMurray DN. Spleen morphology and lymphoproliferative activity in short photoperiod exposed hamsters. In: Franschini F, Reiter RJ, editors. Role of Melatonin and Pineal Peptides in Neuro-immunomodulations. New York: Plenum Publishing, 1991: 19-25.
121. Poon AM, Ayre EA, Song Y, Pang SF. Melatonin implant decreases the density of [125I]iodomelatonin binding sites in the chicken spleen. Biol Signals 1994; 3(6):278-287.
122. Giannessi F, Bianchi F, Dolfi A, Lupetti M. Changes in the chicken bursa of Fabricius and immune response after treatment with melatonin. In Vivo 1992; 6(5):507-512.
123. del Gobbo V, Libri V, Villani N, Calio R, Nistico G. Pinealectomy inhibits interleukin-2 production and natural killer activity in mice. Int J Immunopharmacol 1989; 11(5):567-573.
124. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann N Y Acad Sci 2000; 917:376-386.
125. Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM. Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res 2000; 28(4):193-202.
126. Currier NL, Sun LZ, Miller SC. Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity. J Neuroimmunol 2000; 104(2):101-108.
127. Maestroni GJ, Sulli A, Pizzorni C, Villaggio B, Cutolo M. Melatonin in rheumatoid arthritis: synovial macrophages show melatonin receptors. Ann N Y Acad Sci 2002; 966:271-275.
128. Kuci S, Becker J, Verr G. Circadian variations of the immunomodulatory role of the pineal gland. Neuro-endocrinol Lett 1983; 10:65-79.
129. Shafer LL, McNulty JA, Young MR. Assessment of melatonin's ability to regulate cytokine production by macrophage and microglia cell types. J Neuroimmunol 2001; 120(1-2):84-93.
130. Brennan CP, Hendricks GL III, El-Sheikh TM, Mashaly MM. Melatonin and the enhancement of immune responses in immature male chickens. Poult Sci 2002; 81(3):371-375.
131. Kuhlwein E, Irwin M. Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression. J Neuroimmunol 2001; 117(1-2):51-57.
132. Demas GE, Klein SL, Nelson RJ. Reproductive and immune responses to photoperiod and melatonin are linked in Peromyscus subspecies. J Comp Physiol [A] 1996; 179(6):819-825.
133. Drazen DL, Jasnow AM, Nelson RJ, Demas GE. Exposure to short days, but not short-term melatonin, enhances humoral immunity of male Syrian hamsters (Mesocricetus auratus). J Pineal Res 2002; 33(2):118-124.
134. Demas GE, Nelson RJ. Exogenous melatonin enhances cell-mediated, but not humoral, immune function in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 1998; 13(3):245-252.
135. Bentley GE, Demas GE, Nelson RJ, Ball GF. Melatonin, immunity and cost of reproductive state in male European starlings. Proc R Soc Lond B Biol Sci 1998; 265(1402):1191-1195.
136. Maestroni GJ. T-helper-2 lymphocytes as a peripheral target of melatonin. J Pineal Res 1995; 18(2):84-89.
137. Maestroni GJ, Conti A, Pierpaoli W. Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism. Immunology 1988; 63(3):465-469.
138. Maestroni GJ. The photoperiod transducer melatonin and the immune-hematopoietic system. J Photochem Photobiol B 1998; 43(3):186-192.
139. Maestroni GJ. The immunotherapeutic potential of melatonin. Expert Opin Investig Drugs 2001; 10(3):467-476.
140. Raghavendra V, Singh V, Kulkarni SK, Agrewala JN. Melatonin enhances Th2 cell mediated immune responses: lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists. Mol Cell Biochem 2001; 221(1-2):57-62.
141. Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM. Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 1997; 159(2):574-581.
142. Maestroni GJ. MLT and the immune-hematopoietic system. Adv Exp Med Biol 1999; 460:395-405.
143. 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; 17(4):164-169.
144. Poeggeler B, Saarela S, Reiter RJ, Tan DX, Chen LD, Manchester LC, Barlow-Walden LR. Melatonin-a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci 1994; 738:419-420.
145. Reiter RJ, Maestroni GJ. Melatonin in relation to the antioxidative defense and immune systems: possible implications for cell and organ transplantation. J Mol Med 1999; 77(1):36-39.
146. Cuzzocrea S, Tan DX, Costantino G, Mazzon E, Caputi AP, Reiter RJ. The protective role of endogenous melatonin in carrageenan-induced pleurisy in the rat. FASEB J 1999; 13(14):1930-1938.
147. Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabo C. Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 1997; 23(2):106-116.
148. El-Sokkary GH, Reiter RJ, Cuzzocrea S, Caputi AP, Hassanein AF, Tan DX. Role of melatonin in reduction of lipid peroxidation and peroxynitrite formation in non-septic shock induced by zymosan. Shock 1999; 12(5):402-408.
149. Mohan N, Sadeghi K, Reiter RJ, Meltz ML. The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B. Biochem Mol Biol Int 1995; 37(6):1063-1070.
150. Chuang JI, Mohan N, Meltz ML, Reiter RJ. Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen. Cell Biol Int 1996; 20(10):687-692.
151. Lapin V. Influence of simultaneous pinealectomy and thymectomy on the growth and formation of metastases of the Yoshida sarcoma in rats. Exp Pathol (Jena) 1974; 9(1-2):108-112.
152. Bindoni M, Jutisz M, Ribot G. Characterization and partial purification of a substance in the pineal gland which inhibits cell multiplication in vitro. Biochim Biophys Acta 1976; 437(2):577-588.
153. Nelson RJ, Blom JM. Photoperiodic effects on tumor development and immune function. J Biol Rhythms 1994; 9(3-4):233-249.
154. Kinsey SG, Prendergast BJ, Nelson RJ. Photoperiod and stress affect wound healing in Siberian hamsters. Physiol Behav 2003; 78:205-211.
155. Rojas IG, Padgett DA, Sheridan JF, Marucha PT. Stress-induced susceptibility to bacterial infection during cutaneous wound healing. Brain Behav Immun 2002; 16(1):74-84.
156. Bilbo SD, Drazen DL, Quan N, He L, Nelson RJ. Short day lengths attenuate the symptoms of infection in Siberian hamsters. Proc R Soc Lond B Biol Sci 2002; 269(1490):447-454.
157. Nava F, Calapai G, Facciola G, Cuzzocrea S, Giuliani G, De Sarro A, Caputi AP. Melatonin effects on inhibition of thirst and fever induced by lipopolysaccharide in rat. Eur J Pharmacol 1997; 331(2-3):267-274.
158. Raghavendra V, Agrewala JN, Kulkarni SK. Role of centrally administered melatonin and inhibitors of COX and NOS in LPS-induced hyperthermia and adipsia. Prostaglandins Leukot Essent Fatty Acids 1999; 60(4):249-253.
159. Bilbo SD, Nelson RJ. Melatonin regulates energy balance and attenuates fever in Siberian hamsters. Endocrinology 2002; 143(7):2527-2533.
160. Prendergast BJ, Hotchkiss AK, Bilbo SD, Kinsey SG, Nelson RJ. Photoperiodic adjustments in immune function protect Siberian hamsters from lethal endotoxemia. J Biol Rhythms 2003; 18:51-62.
161. Maestroni GJ. Melatonin as a therapeutic agent in experimental endotoxic shock. J Pineal Res 1996; 20(2):84-89.
162. Sacco S, Aquilini L, Ghezzi P, Pinza M, Guglielmotti A. Mechanism of the inhibitory effect of melatonin on tumor necrosis factor production in vivo and in vitro. Eur J Pharmacol 1998; 343(2-3):249-255.
163. Baykal A, Iskit AB, Hamaloglu E, Oguz Guc M, Hascelik G, Sayek I. Melatonin modulates mesenteric blood flow and TNFalpha concentrations after lipopolysaccharide challenge. Eur J Surg 2000; 166(9):722-727.
164. Maestroni GJ. The immunoneuroendocrine role of melatonin. J Pineal Res 1993; 14(1):1-10.
165. Maestroni GJ. Therapeutic potential of melatonin in immunodeficiency states, viral diseases, and cancer. Adv Exp Med Biol 1999; 467:217-226.
166. Prendergast BJ, Nelson RJ. Spontaneous "regression" of enhanced immune function in a photoperiodic rodent Peromyscus maniculatus. Proc R Soc Lond B Biol Sci 2001; 268(1482):2221-2228.
167. Brainard GC, Knobler RL, Podolin PL, Lavasa M, Lublin FD. Neuroimmunology: modulation of the hamster immune system by photoperiod. Life Sci 1987; 40(13):1319-1326.
168. Chougnet C, Deloron P, Lepers JP, Tallet S, Rason MD, Astagneau P, Savel J, Coulanges P. Humoral and cell-mediated immune responses to the Plasmodium falciparum antigens PF155/RESA and CS protein: seasonal variations in a population recently reexposed to endemic malaria. Am J Trop Med Hyg 1990; 43(3):234-242.
169. Glezen WP, Payne AA, Snyder DN, Downs TD. Mortality and influenza. J Infect Dis 1982; 146:313-321.
170. Pietinalho A, Hiraga Y, Hosoda Y, Lofroos AB, Yamaguchi M, Selroos O. The frequency of sarcoidosis in Finland and Hokkaido, Japan. A comparative epidemiological study. Sarcoidosis 1995; 12(1):61-67.
171. Dagan R, Engelhard D, Piccard E, Engelhard D. Epidemiology of invasive childhood pneumococcal infections in Israel. JAMA 1992; 268:3328-3332.
172. Cowart RP, Boessen CR, Kliebenstein JB. Patterns associated with season and facilities for atrophic rhinitis and pneumonia in slaughter swine. J Am Vet Med Assoc 1992; 200(2):190-193.
173. Bamford CR, Sibley WA, Thies C. Seasonal variation of multiple sclerosis exacerbations in Arizona. Neurology 1983; 33(6):697-701.
174. Tang D, Santella RM, Blackwood AM, Young TL, Mayer J, Jaretzki A, Grantham S, Tsai WY, Perera FP. A molecular epidemiological case-control study of lung cancer. Cancer Epidemiol Biomarkers Prev 1995; 4(4):341-346.
175. Suss J, Schafer J, Sinnecker H, Webster RG. Influenza virus subtypes in aquatic birds of eastern Germany. Arch Virol 1994; 135(1-2):101-114.
176. Chandra S, Agarwal GP, Singh SP, Saxena AK. Seasonal changes in a population of Menacanthus eurysternus (Mallophaga, Amblycera) on the common myna Acridotheres tristis. Int J Parasitol 1990; 20(8):1063-1065.
177. Baker NF, Fisk RA. Seasonal occurrence of infective nematode larvae in California Sierra foothill pastures grazed by cattle. Am J Vet Res 1986; 47(8):1680-1685.
178. Waid DD, Pence DB, Warren RJ. Effects of season and physical condition on the gastrointestinal helminth community of white-tailed deer from the Texas Edwards Plateau. J Wildl Dis 1985; 21(3):264-273.
179. Forrester DJ, Porter JH, Belden RC, Frankenberger WB. Lungworms of feral swine in Florida. J Am Vet Med Assoc 1982; 181(11):1278-1280.
180. Talleklint L., Jaenson T.G, Mather T.N. Seasonal variation in the capacity of the bank vole to infect larval ticks (Acari: Ixodidae) with the Lyme disease spirochete, Borrelia burgdorferi. J Med Entomol 1993; 30(4):812-815.