TESTOSTERONE-INDUCED SUPPRESSION OF SELF-HEALING PLASMODIUM-CHABAUDI MALARIA - AN EFFECT NOT MEDIATED BY ANDROGEN RECEPTORS

被引:27
作者
BENTEN, WPM [1 ]
WUNDERLICH, F [1 ]
MOSSMANN, H [1 ]
机构
[1] MAX PLANCK INST IMMUNBIOL,W-7800 FREIBURG,GERMANY
关键词
D O I
10.1677/joe.0.1350407
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study investigates whether androgen receptors (AR) mediate the suppressive effect of testosterone on self-healing Plasmodium chabaudi malaria. Our data show the following. (1) Female and castrated male mice of the inbred strain C57BL/10 self-heal and survive infections when challenged with 10(6) p. chabaudi-parasitized erythrocytes. However, self-healing is prevented when circulating testosterone levels are high as in intact males or in females and castrated males pretreated with 0.9 mg testosterone twice a week for 3 weeks. (2) The lethal outcome of P. chabaudi in intact males is not affected by different doses of AR blockers such as cyproterone acetate, cyproterone, flutamide and nilutamide when applied at least 3 weeks before infection and during infection. Also, these AR blockers do not impair the testosterone-induced lethal outcome of infections in testosterone-treated females and castrated males. (3) Tfm mice possessing mutant non-functional ARs and normal 'male' testosterone levels succumb to infection with P. chabaudi. However, the corresponding wild-type mice possessing functioning ARs are able to resist P. chabaudi infections at low circulating testosterone levels. (4) In contrast to testosterone, testosterone metabolites such as 5alpha-dihydrotestosterone, 5beta-dihydrotestosterone, androsterone and 1-dehydrotestosterone cannot suppress self-healing in castrated male B10 mice. Our data suggest that testosterone suppresses the development of protective immunity against P. chabaudi malaria, and that this immunosuppressive effect of testosterone is not primarily mediated by the classical AR response.
引用
收藏
页码:407 / 413
页数:7
相关论文
共 26 条
[1]   SEX-HORMONES AND THE COURSE OF PARASITIC INFECTION [J].
ALEXANDER, J ;
STIMSON, WH .
PARASITOLOGY TODAY, 1988, 4 (07) :189-193
[2]   DIHYDROTESTOSTERONE EXERTS A DEPRESSIVE INFLUENCE ON THE PRODUCTION OF INTERLEUKIN-4 (IL-4), IL-5, AND GAMMA-INTERFERON, BUT NOT IL-2 BY ACTIVATED MURINE T-CELLS [J].
ARANEO, BA ;
DOWELL, T ;
DIEGEL, M ;
DAYNES, RA .
BLOOD, 1991, 78 (03) :688-699
[3]   TESTOSTERONE-INDUCED ABROGATION OF SELF-HEALING OF PLASMODIUM-CHABAUDI MALARIA IN B10 MICE - MEDIATION BY SPLEEN-CELLS [J].
BENTEN, WPM ;
BETTENHAEUSER, U ;
WUNDERLICH, F ;
VANVLIET, E ;
MOSSMANN, H .
INFECTION AND IMMUNITY, 1991, 59 (12) :4486-4490
[4]  
BENTEN WPM, 1992, IN PRESS EXPT PARASI
[5]   REGULATION OF MURINE LYMPHOKINE PRODUCTION INVIVO .2. DEHYDROEPIANDROSTERONE IS A NATURAL ENHANCER OF INTERLEUKIN-2 SYNTHESIS BY HELPER T-CELLS [J].
DAYNES, RA ;
DUDLEY, DJ ;
ARANEO, BA .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1990, 20 (04) :793-802
[6]   INVOLVEMENT OF T-CELLS IN MALARIA IMMUNITY - IMPLICATIONS FOR VACCINE DEVELOPMENT [J].
GOOD, MF ;
MILLER, LH .
VACCINE, 1989, 7 (01) :3-9
[7]   REGULATION OF THE IMMUNE-SYSTEM BY SEX STEROIDS [J].
GROSSMAN, CJ .
ENDOCRINE REVIEWS, 1984, 5 (03) :435-455
[8]   EFFECTS OF TESTOSTERONE ON BLOOD LEUKOCYTES IN PLASMODIUM-BERGHEI-INFECTED MICE [J].
KAMIS, AB ;
IBRAHIM, JB .
PARASITOLOGY RESEARCH, 1989, 75 (08) :611-613
[9]  
KEMP CJ, 1989, CANCER RES, V49, P5044
[10]  
KIHARA K, 1990, CANCER RES, V50, P2848