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Abstract
In the present study, we focused on the interactions between reproductive system and immune systems response for aging. In the present study, we measured the proinflammatory cytokines to evaluate the response of the immune system, as the proinflammatory cytokines play a central role in mediating cellular and physiological responses and their levels may reflect immune system effectiveness. The present study was carried out on eighty-four albino rats, which subdivided into forty-eight female albino rats and thirty-sex male albino rats. Each group was further subdivided into adult (2-6 months) and old (18-22 months) subgroups Both adult and old rats were subdivided into: Control group: consists of sham-operated rats injected subcutaneously with sesame oil for 14 days. Gonadectomized group: consists of ovariectomized or orchidectomized rats, which were injected with sesame oil. Gonadectomized rats on hormonal replacement therapy HRT: the ovariectomized rats were subdivided into two groups, one group was given HRT in the form of estrogen and the other was given HRT in the form of progesterone, while the orchidectomized rats were given testosterone. The results of the present study demonstrated a significant increase in the serum levels of IL-1β, IL-6 and TNF-α two weeks after ovariectomy in adult female group. Moreover, treatment with physiological dose of either estrogen or progesterone caused significant decrease in the levels of IL-1 β, IL-6 and TNF-α when compared with the ovariectomized groups. There is no significant differences between the effects of estrogen and progesterone on the serum levels of IL-1β, IL-6 and TNF-α and no significant differences in the levels of cytokines between the treated groups by either estrogen or progesterone and control groups. Moreover, our results revealed that the serum levels of the IL-6 and TNF-α were increased significantly after ovariectomy in old female group and these levels returned to the basal control levels of the old rats after replacement with physiological dose of either E2 or P. There is no difference between the effect of E2 and P. The IL-1β was not affected by either ovariectomy or hormonal replacement therapy. In addition, the levels of IL-1β were low in the control old group when compared with those of the control adult rats. Collectively, the above results suggested an inhibitory effect for estrogen (E2) and progesterone (P) on the spontaneous secretion of proinflammatory cytokines (IL-6 and TNF-α) in adult and old rats. However the IL-1 β was not affected by female sex hormones in old groups. The hormonal replacement therapy caused depression of the elevated levels of the IL-6 and TNF-α to the levels of the control female rats. Moreover, the present study reveled that the levels of IL-6 and TNF-α were significantly higher in the old ovariectomized rats treated with either estrogen or progesterone when compared with adult ovariectomized rats treated with either estrogen or progesterone respectively. While the levels of IL-1β showed nonsignificant difference between the adult and old ovariectomized female rats treated by either E2 or P. Therefore, the replacement therapy in aged rats has limited effects because there are other factors that also may be involved in the regulation of the proinflammatory cytokines with age. With regard to the effect of male sex hormones on the production of proinflammatory cytokines, our results showed a significant increase in the serum levels of IL-1β, IL-6 and TNF-α 2 weeks after orchidectomy in adult male group when compared with the control. Moreover, treatment with physiological dose of testosterone caused significant decrease in the levels of IL-1, IL-6 and TNF-α when compared with the orchidectomized groups. There are nonsignificant differences in the cytokines levels between the groups treated with T and those of the control groups.In the present study to asses the role of adrenlpause in old age on the proinflammatory marker we performed orchidectomy in the old male rats, also the effect of testosterone replacement was evaluated. The results revealed significant increase in the levels of IL-6 and TNF-α in the ODX group when compared with the control. The testosterone treatment resulted in significant decrease in the elevated level of IL-6 and TNF-α to the level of the old control rats. Neither the orchidectomy nor the testosterone replacement caused significant change in the IL-1β levels. These results demonstrated a significant role for male sex hormone in regulation of the proinflammatory cytokines (IL-6 and TNF-α) production. The hormonal replacement therapy caused depression of the elevated levels of the IL-6 and TNF-α to the levels of the control male rats. Moreover, the present study indicated that the old orchidectomized rats treated with testosterone have significantly higher levels of IL-6 and TNF-α when compared with adult orchidectomized rats treated with testosterone. While the levels of IL-1β showed a nonsignificant differences between the adult and old orchidectomized rats treated with T. Therefore, the replacement therapy in aged rats has limited effects, may be due to the presence of many factors that involved in regulation of sex hormone with age. Moreover, we try to detect the gender difference in proinflammatory cytokines production and evaluate the role of sex hormone in this difference. Our results revealed that adult control males and old control male had higher levels of IL-1β, IL-6 and TNF-α than the adult control females and old control female respectively. However, after gonadectomy the adult OVX females and old OVX females becomes higher for IL-6 and TNF-α than the adult ODX males and old ODX males respectively. The levels of IL-1β are higher in adult ODX males and old ODX males than in adult OVX females and old OVX females respectively.