ABSTRACT
The aims of this study were, first, to explore the differences in the expression of Th1/Th2 cytokines and of steroid receptors in spleen of intact and gonadectomized mice of both sexes; second, to evaluate the effect of estradiol (E2), progesterone (P4) and testosterone (T) on cytokine production and lymphocyte proliferation, and third, to determine the percentage of spleen cell subpopulations in both sexes. Results indicated dimorphic expression of IFN-gamma and IL-4, which was affected by gonadectomy. CD4+ T lymphocytes were the most frequent type of cell in the spleen, followed by B lymphocytes (CD19+). Interestingly, there was no dimorphic pattern of cell subtypes, and gonadectomy had no effect. Regarding lymphocyte proliferation, E2 inhibited both cells of male (19.51%) and female (24.62%). P4 diminished lymphocyte proliferation by 22% in cells of female and had no effect on cells of male. It is very interesting to note that the sex steroid receptors mRNA was highly expressed in all splenocytes, and that this expression was dimorphic. However, flow cytometry analysis confirmed that only expression of progesterone receptor was dimorphic. This dimorphic pattern was, however, only seen in lymphocytes. Present evidence indicates that sex steroids are capable of affecting crucial immune system functions dimorphically.
Subject(s)
Cytokines/metabolism , Gonadal Steroid Hormones/pharmacology , Lymphocytes/cytology , Lymphocytes/immunology , Receptors, Cell Surface/metabolism , Sex Characteristics , Animals , Cell Proliferation/drug effects , Female , Flow Cytometry , Gene Expression Regulation/drug effects , Lymphocytes/drug effects , Male , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Cell Surface/genetics , Spleen/cytology , Spleen/drug effects , Spleen/metabolism , Th1 Cells/cytology , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/cytology , Th2 Cells/drug effects , Th2 Cells/immunologyABSTRACT
The aim of this work was to investigate the role of progesterone during Taenia crassiceps cysticercosis, and the immunological mechanisms involved in its effects, by relating progesterone treatment to whole parasite counts, to host humoral and cellular immune response, to the presence or absence of nuclear receptors to sex steroids in splenocytes, and to serum sex steroid levels in infected mice of both genders. Progesterone treatment increased parasite loads two-fold in females and three-fold in males compared with control mice. The expression of the Th2 cytokine profile (IL-4, IL-6 and IL-10) was markedly increased in infected mice of both genders, while progesterone treatment returned this expression to basal levels. However, the Th1 cytokine profile (IFN-gamma and TNF-alpha) was not affected by infection, whilst progesterone treatment increased the expression of both cytokines two-fold compared to uninfected, infected and placebo-treated mice. Testosterone serum levels decreased in infected male mice by 95%, and treatment with progesterone did not affect them. In females, no change in testosterone levels was observed. Progesterone levels increased three-fold only in progesterone-treated infected mice of both sexes, while estradiol levels in female and male progesterone-treated infected mice increased two-fold compared to infected control mice. The infection markedly induced the expression of progesterone receptor (PR) isoforms A and B in splenocytes of infected mice of both genders (five-fold). Metabolism of progesterone to estradiol was demonstrated by the use of the anti-estrogen tamoxifen, which reduced parasite loads 100% in infected mice of both sexes treated with progesterone. These results suggest that progesterone, possibly through its metabolism to estradiol, affects establishment, growth and reproduction of the helminth parasite T. crassiceps.
