Sex Differences in Immunology and Immunosuppression

There is indirect evidence of sex differences in immunology. Women have a higher incidence of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythemato-sus. The influence of sex hormones on the immune system may provide insight into these immuno-logical disorders. For example, estrogen stimulates both humoral and cell-mediated immunity, whereas testosterone has the opposite effect (126). Therefore, it is not surprising that there is sex-dependent variability in response to immunosuppressive agents.

Two groups of agents have been investigated for sex differences: corticosteroids and cytotoxic T-cell-suppressing agents. Women have been shown to have greater total body clearance of methylprednisolone than men have and also are more sensitive to suppression of endogenous cortisol production (127). The IC50 value for cortisol suppression was 17 times lower in women than in men. However, these pharma-cokinetic and pharmacodynamic sex differences were offsetting, such that the net response to a given dose of methylprednisolone was similar in both men and women. In another study, men were found to have a higher oral clearance and larger volume of distribution of prednisolone compared to women, but these pharmacokinetic changes did not result in overall response differences (128).

In vivo information on cytotoxic T-cell-suppressing agents is very limited, but men and women have not been found to have sex-dependent differences in inhibition of lymphocyte proliferation, (129). Although numerous studies have postulated the presence of sex differences based on a higher incidence of organ rejection and increased mortality in women, it is not clear that these observations are due to sex differences (130). In an in vitro study, it was found that cyclosporine was metabolized faster by small intestinal microsomes from females, but this finding was based on only four female samples (131).

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