1921
Volume 73, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Reproductive physiology and endocrinology change with the onset of illness and injury in a variety of species, including humans. To assess the human reproductive endocrine response to malaria, serial serum samples were collected from 8 male and 9 female residents of Honduras infected with (plus 19 male and 23 female healthy age-matched controls) and were analyzed for associations between testosterone, parasitemia, and cytokine levels. Because testosterone has been negatively associated with measures of immune function under various circumstances, it was hypothesized that testosterone would be directly associated with parasitemia and inversely associated with proinflammatory cytokine levels. The findings presented here suggest that 1) testosterone levels are positively associated with parasitemia in adult males, and 2) males infected with exhibit significantly lower testosterone levels and significantly higher cortisol levels than healthy individuals. Depressed androgen levels during physiologic perturbations may be an advantageous, adaptive host response to ameliorate immunosuppression by higher testosterone levels and to curb the use of energetic resources for metabolically expensive anabolic functions.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2005.73.178
2005-07-01
2018-12-13
Loading full text...

Full text loading...

/deliver/fulltext/14761645/73/1/0730178.html?itemId=/content/journals/10.4269/ajtmh.2005.73.178&mimeType=html&fmt=ahah

References

  1. Trigg PI, Kondrachine AV, 1998. The current global malaria situation. Sherman PW, ed. Malaria: Parasite Biology, Pathogenesis, and Protection. Washington, DC: ASM Press, 11–24.
  2. World Health Organization, 1997. World malaria situation in 1994: population at risk. Wkly Epidemiol Rec 72 : 269–276. [Google Scholar]
  3. Muehlenbein MP, 2004. Testosterone-Mediated Immune Function: An Energetic Allocation Mechanism Evaluated in Human and Non-Human Primate Males. Ph.D. Thesis, Department of Anthropology, Yale University.
  4. Wedekind C, Folstad I, 1994. Adaptive or nonadaptive immuno-suppression by sex-hormones. Am Nat 143 : 936–938. [Google Scholar]
  5. Sheldon BC, Verhulst S, 1996. Ecological immunology: costly parasite defenses and trade-offs in evolutionary ecology. Trends Ecol Evol 11 : 317–321. [Google Scholar]
  6. Folstad I, Nilssen AC, Halvorsen O, Andersen J, 1989. Why do male reindeer (Rangifer tarandus tarandus) have higher abundance of second and third instar larvae of Hypoderma tarandi than females? Oikos 55 : 87–92. [Google Scholar]
  7. Tiuria R, Horii Y, Makimura S, Ishikawa N, Tsuchiya K, Nawa Y, 1995. Effect of testosterone on the mucosal defence against intestinal helminths in Indian soft-furred rats, Millardia meltada with reference to goblet and mast cell responses. Parasite Immunol 17 : 479–484. [Google Scholar]
  8. Olsen NJ, Kovacs WJ, 1996. Gonadal steroids and immunity. Endocr Rev 17 : 369–384. [Google Scholar]
  9. Poulin R, 1996. Sexual inequalities in helminth infections: a cost of being a male? Am Nat 147 : 287–295. [Google Scholar]
  10. Zuk M, McKean KA, 1996. Sex differences in parasite infections: patterns and processes. Int J Parasitol 26 : 1009–1023. [Google Scholar]
  11. Moore SL, Wilson K, 2002. Parasites as a viability cost of sexual selection in natural populations of mammals. Science 297 : 2015–2018. [Google Scholar]
  12. Weatherhead PJ, Metz KJ, Bennett GF, Irwin RE, 1993. Parasite faunas, testosterone and secondary sexual traits in male red-winged blackbirds. Behav Ecol Sociobiol 33 : 13–23. [Google Scholar]
  13. Saino N, Moller AP, 1994. Secondary sexual characters, parasites and testosterone in the barn swallow, Hirundo rustica. Anim Behav 48 : 1325–1333. [Google Scholar]
  14. Saino N, Moller AP, Bolzern AM, 1995. Testosterone effects on the immune system and parasite infestations in the barn swallow (Hirundo rustica): an experimental test of the immunocompetence hypothesis. Behav Ecol 6 : 397–404. [Google Scholar]
  15. Hasselquist D, Marsh JA, Sherman PW, Wingfield JC, 1999. Is avian humoral immunocompetence suppressed by testosterone? Behav Ecol Sociobiol 45 : 167–175. [Google Scholar]
  16. Duffy DL, Ball GF, 2002. Song predicts immunocompetence in male European starlings (Sturnus vulgaris). Proc R Soc Lond B Biol Sci 269 : 847–852. [Google Scholar]
  17. Weinstein Y, Bercovich Z, 1981. Testosterone effects on bone marrow, thymus and suppressor T cells in the (NZB x NZW) F1 mice: its relevance to autoimmunity. J Immunol 126 : 998–1002. [Google Scholar]
  18. Schuurs AHWM, Verheul HAM, 1990. Effects of gender and sex steroids on the immune response. J Steroid Biochem Mol Biol 35 : 157–172. [Google Scholar]
  19. Olsen NJ, Watson MB, Henderson GS, Kovacs WJ, 1991. Androgen deprivation induces phenotypic and functional changes in the thymus of adult mice. Endocrinology 129 : 2471–2476. [Google Scholar]
  20. Folstad I, Karter AJ, 1992. Parasites, bright males and the immunocompetence handicap. Am Nat 139 : 603–622. [Google Scholar]
  21. Benten WP, Wunderlich F, Herrmann R, Kuhn-Velten WN, 1993. Testosterone-induced compared with oestradiol-induced immunosuppression against Plasmodium chabaudi malaria. J Endocrinol 139 : 487–494. [Google Scholar]
  22. Hadid R, Spinedi E, Daneva T, Grau G, Gaillard RC, 1995. Repeated endotoxin treatment decreases immune and hypo-thalamo-pituitary-adrenal axis responses—effects of orchiectomy and testosterone therapy. Neuroendocrinology 62 : 348–355. [Google Scholar]
  23. Zuk M, Johnsten TS, Maclarty T, 1995. Endocrine-immune interactions, ornaments and mate choice in red jungle fowl. Proc R Soc Lond B Biol Sci 260 : 205–210. [Google Scholar]
  24. Duffy DL, Bentley GE, Drazen DL, 2000. Effects of testosterone on cell-mediated and humoral immunity in non-breeding adult European starlings. Behav Ecol 11 : 654–662. [Google Scholar]
  25. Grossman CJ, Roselle GA, Mendenhall CL, 1991. Sex steroid regulation of autoimunity. J Steroid Biochem Mol Biol 40 : 649– 659. [Google Scholar]
  26. Chao TC, Van Alten PJ, Walter RJ, 1994. Steroid sex hormones and macrophage function: modulation of reactive oxygen intermediates and nitrite release. Am J Reprod Immunol 32 : 43–52. [Google Scholar]
  27. Chao TC, Van Alten PJ, Greager JA, Walter RJ, 1995. Steroid sex hormones regulate the release of tumor necrosis factor by macrophages. Cell Immunol 160 : 43–49. [Google Scholar]
  28. Grossman CJ, 1995. The role of sex steroids in immune system regulation. Grossman CJ, ed. Bilateral Communication between the Endocrine and Immune Systems. New York: Springer-Verlag, 1–11.
  29. Benten WP, Ulrich P, Kuhn-Velten WN, Vohr HW, Wunderlich F, 1997. Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence after withdrawal of testosterone. J Endocrinol 153 : 275–281. [Google Scholar]
  30. Straub RH, Cutolo M, 2001. Involvement of the hypothalamic-pituitary-adrenal/gonadal axis and the peripheral nervous system in rheumatoid arthritis: viewpoint based on a systemic pathogenetic role. Arthritis Rheum 44 : 493–507. [Google Scholar]
  31. Wunderlich F, Benten WP, Lieberherr M, Guo Z, Stamm O, Wrehlke C, Sekeris CE, Mossmann H, 2002. Testosterone signaling in T cells and macrophages. Steroids 67 : 535–538. [Google Scholar]
  32. Palmer CJ, Makler M, Klaskala WI, Lindo JF, Baum MK, Ager AL, 1998. Increased prevalence of Plasmodium falciparum malaria in Honduras, Central America. Rev Panam Salud Publica 4 : 40–42. [Google Scholar]
  33. SAS Institute Inc, 2001. SAS System for Windows. Cary, NC: SAS Institute Inc.
  34. Elenkov IJ, Papanicolaou DA, Wilder RL, Chrousos GP, 1996. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Assoc Am Physicians 108 : 374–381. [Google Scholar]
  35. Norbiato G, Bevilacqua M, Vago T, Taddei A, Clerici M, 1997. Glucocorticoids and the immune function in the human immunodeficiency virus infection: a study in hypercortisolemic and cortisol-resistant patients. J Clin Endocrinol Metab 82 : 3260–3263. [Google Scholar]
  36. Elenkov IJ, Chrousos GP, 1999. Stress, cytokine patterns and susceptibility to disease. Baillieres Best Pract Res Clin Endocrinol Metab 13 : 583–595. [Google Scholar]
  37. Turnbull AV, Rivier CL, 1999. Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79 : 1–71. [Google Scholar]
  38. Doerr P, Pirke KM, 1976. Cortisol-induced suppression of plasma testosterone in normal adult males. J Clin Endocrinol Metab 43 : 622–629. [Google Scholar]
  39. Bambino TH, Hsueh AJ, 1981. Direct inhibitory effect of gluco-corticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro. Endocrinology 108 : 2142–2148. [Google Scholar]
  40. Faul F, Erdfelder E, 1992. GPower: a priori, post-hoc, and compromise power analyses for MS-DOS. Bonn, FRG: Bonn University, Department of Psychology.
  41. Lehmann EL, 1975. Nonparametrics. Statistical Methods Based on Ranks. San Francisco: Holden-Day.
  42. Park JW, Park SH, Yeom JS, Huh AJ, Cho YK, Ahn JY, Min GS, Song GY, Kim YA, Ahn SY, Woo SY, Lee BE, Ha EH, Han HS, Yoo K, Seoh JY, 2003. Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without thrombocytopenia. Ann Trop Med Parasitol 97 : 339–344. [Google Scholar]
  43. Karunaweera ND, Carter R, Grau GE, Mendis KN, 1998. Demonstration of anti-disease immunity to Plasmodium vivax malaria in Sri Lanka using a quantitative method to assess clinical disease. Am J Trop Med Hyg 58 : 204–210. [Google Scholar]
  44. Mendis KN, Carter R, 1992. The role of cytokines in Plasmodium vivax malaria. Mem Inst Oswaldo Cruz 87 : 51–55. [Google Scholar]
  45. Seoh JY, Khan M, Park SH, Park HK, Shin MH, Ha EH, Lee BE, Yoo K, Han HS, Oh S, Wi JH, Hong CK, Oh CH, Kim YA, Park JW, 2003. Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without hyperpyrexia. Am J Trop Med Hyg 68 : 102–106. [Google Scholar]
  46. Mendis KN, Naotunne TD, Karunaweera ND, Del Giudice G, Grau GE, Carter R, 1990. Anti-parasite effects of cytokines in malaria. Immunol Lett 25 : 217–220. [Google Scholar]
  47. Stevenson MM, Tam MF, Belosevic M, Meide Pvd, Podoba JE, 1990. Role of endogenous gamma interferon in host response to infection with blood-stage Plasmodium chabaudi AS. Infect Immun 58 : 3225–3232. [Google Scholar]
  48. Artavanis-Tsakonas K, Tongren JE, Riley EM, 2003. The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. Clin Exp Immunol 133 : 145–152. [Google Scholar]
  49. Butcher GA, Garland T, Ajdukiewicz AB, Clark IA, 1990. Serum tumor necrosis factor associated with malaria in patients in the Solomon Islands. Trans R Soc Trop Med Hyg 84 : 658–661. [Google Scholar]
  50. Brown AE, Teja-Isavadharm P, Webster HK, 1991. Macrophage activation in vivax malaria: fever is associated with increased levels of neopterin and interferon-gamma. Parasite Immunol 13 : 673–679. [Google Scholar]
  51. Boutlis CS, Lagog M, Chaisavaneeyakorn S, Misukonis MA, Bockarie MJ, Mgone CS, Wang Z, Morahan G, Weinberg JB, Udhayakumar V, Anstey NM, 2003. Plasma interleukin-12 in malaria-tolerant papua new guineans: inverse correlation with Plasmodium falciparum parasitemia and peripheral blood mononuclear cell nitric oxide synthase activity. Infect Immun 71 : 6354–6357. [Google Scholar]
  52. Praba-Egge AD, Montenegro S, Arevalo-Herrera M, Hopper T, Herrera S, James MA, 2003. Human cytokine responses to meso-endemic malaria on the Pacific Coast of Colombia. Ann Trop Med Parasitol 97 : 327–337. [Google Scholar]
  53. Fedigan LM, Zohar S, 1997. Sex differences in mortality of Japanese macaques: Twenty-one years of data from the Arashiyama West population. Am J Phys Anthropol 102 : 161–175. [Google Scholar]
  54. Travi BL, Osorio Y, Melby PC, Chandrasekar B, Arteaga L, Saravia NG, 2002. Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. Infect Immun 70 : 2288–2296. [Google Scholar]
  55. Brabin L, 1990. Sex differentials in susceptibility to lymphatic filariasis and implications for maternal child immunity. Epidemiol Infect 105 : 335–353. [Google Scholar]
  56. Ayala SC, Spain JL, 1976. A population of Plasmodium colombiense sp. N. in the iguanid lizard, Anolis auratus. J Parasitol 62 : 177–189. [Google Scholar]
  57. Schall JJ, Vogt SP, 1993. Distribution of malaria in Anolis lizards of the Lupuillo Forest, Puerto Rica: implications for host community ecology. Biotropica 25 : 229–235. [Google Scholar]
  58. Schall JJ, 1996. Malaria parasites in lizards: diversity and ecology. Adv Parasitol 37 : 255–333. [Google Scholar]
  59. Schalk G, Forbes MR, 1997. Male biases in parasitism of mammals. Oikos 78 : 67–74. [Google Scholar]
  60. Klein SL, 2000. The effects of hormones on sex differences in infection: from genes to behavior. Neurosci Biobehav Rev 24 : 627–638. [Google Scholar]
  61. Zuk M, 1996. Disease, endocrine-immune interactions, and sexual selection. Ecology 77 : 1037–1042. [Google Scholar]
  62. Wedekind C, Jakobsen PJ, 1998. Male-biased susceptibility to helminth infection: an experimental test with a copepod. Oikos 81 : 458–462. [Google Scholar]
  63. Eisen RJ, DeNardo DF, 2000. Life history of a malaria parasite (Plasmodium mexicanum) in its host, the western fence lizard (Sceloporus occidentalis): host testosterone as a source of seasonal and among-host variation? J Parasitol 86 : 1041–1045. [Google Scholar]
  64. Kurtis JD, Mtalib R, Onyango FK, Duffy PE, 2001. Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels. Infect Immun 69 : 123–128. [Google Scholar]
  65. Campbell BC, Lukas WD, Campbell KL, 2001. Reproductive Ecology of Male Immune Function and Gonadal Function. Ellison PT, ed. Reproductive Ecology and Human Evolution. New York: Aldine de Gruyter, 159–178.
  66. Cernak I, Savic J, Lazarov A, 1997. Relations among plasma prolactin, testosterone, and injury severity in war casualties. World J Surg 21 : 240–245. [Google Scholar]
  67. Spratt DI, 2001. Altered gonadal steroidogenesis in critical illness: is treatment with anabolic steroids indicated? Best Pract Res Clin Endocrinol Metab 15 : 479–494. [Google Scholar]
  68. Dym M, Orenstein J, 1990. Structure of the male reproductive tract in AIDS patients. Alexander NJ, Gabelnick HL, Spieler JM, eds. Heterosexual Transmission of AIDS. New York: Alan R. Liss, 181–196.
  69. Nadler RD, Manocha AD, McClure HM, 1993. Spermatogenesis and hormone levels in rhesus macaques inoculated with simian immunodeficiency virus. J Med Primatol 22 : 325–329. [Google Scholar]
  70. Soudan B, Tetaert D, Racadot A, Degand P, Boersma A, 1992. Decrease of testosterone level during an experimental African trypanosomiasis: involvement of a testicular LH receptor desensitization. Acta Endocrinol (Copenh) 127 : 86–92. [Google Scholar]
  71. Valenti S, Cuttica CM, Giusti M, Giordano G, 1999. Nitric oxide modulates Leydig cell function in vitro: is this a way of communication between the immune and endocrine system in the testis? Ann N Y Acad Sci 876 : 298–300. [Google Scholar]
  72. Hales DB, 1992. Interleukin-1 inhibits Leydig cell steroidogenesis primarily by decreasing 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 expression. Endocrinology 131 : 2165–2172. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2005.73.178
Loading
/content/journals/10.4269/ajtmh.2005.73.178
Loading

Data & Media loading...

  • Received : 04 Jan 2005
  • Accepted : 25 Feb 2005

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error