Immunomodulatory cytokines in human seminal plasma correlate with immunomodulatory steroids

Abstract

7α-Hydroxy-dehydroepiandrosterone and its 7β-hydroxyepimer, which act as local immunomodulatory agents, dehydroepiandrosterone, cortisol, and major androgens, together with four cytokines—interleukins 2, 4, 10, and IFN-γ, reflecting the activity of TH1 or TH2 cells present in semen, were measured in seminal plasma from 35 male donors. Cortisol, dehydroepiandrosterone, its sulfate, 7-hydroxy-dehydroepiandrosterone epimers, testosterone, and estradiol were also measured in their blood serum. Steroids and interleukins in semen as well as serum steroids and seminal interleukins were mutually correlated to find out whether a relationship between immunomodulatory steroids and cytokines influencing the immune environment does exist. A highly significant ( P<0.001) positive correlation was found between seminal 7β-hydroxy-dehydroepiandrosterone and IFN-γ, while a negative correlation was found between cortisol and IL-10. Highly significant positive correlations were also found between serum 7α-hydroxy-dehydroepiandrosterone and seminal IFN-γ and between serum 7β-hydroxy-dehydroepiandrosterone and seminal IL-2, while a negative correlation was found between serum dehydroepiandrosterone and seminal IL-10. Different and in some instances, even contradictory findings concerning the influence of dehydroepiandrosterone and cortisol on TH1 and TH2 cytokines were observed in seminal plasma as compared to those found by others in serum. The differences can be ascribed to the different environments of mucosal and systemic immunity. Correlations between the levels of steroids and cytokines in seminal plasma did not always correspond to the correlations between given cytokines and hormones in sera. The results, however, are in agreement with our recent finding of an autonomous production of these steroids in the male reproductive tract.