Preliminary studies on the effect of dehydroepiandrosterone (DHEA) on bothconstitutive and phytohaemagglutinin (PHA)-inducible IL-6 and IL-2 mRNA expression and cytokine production in human spleen mononuclear cell suspensions in vitro

In order to gain further insight into the potential immunological benefits of oral administration of DHEA we have examined its effects on the constitu tive and PHA-inducible expression by human spleen cell suspensions in vitro of IL-6 and IL-2. This was studied at both the mRNA and protein levels. Th e quantification of specific mRNA was undertaken using commercially availab le quantitative polymerase chain reaction kits. These studies, which were p erformed on suspensions from six individual spleens, revealed that 10(-5) m DHEA did not impair the expression of IL-6 at either the mRNA or protein l evel, but may have slightly enhanced the latter. In contrast, IL-2 mRNA lev els were increased on most occasions, whilst IL-2 secretion was decreased, albeit slightly. Additional studies revealed that cyclosporin (approx. 10(- 5) m) and dexamethasone (10(-7) m) readily inhibited these responses and th e production of other cytokines, including interferon-gamma and tumour necr osis factor-alpha. These preliminary studies suggest that high doses of DHE A do not readily inhibit the production of IL-6, and indeed other cytokines , by PHA-stimulated secondary human lymphoid tissue suspensions in vitro. T hey may also partially explain the meagre immunomodulatory effects noted in some DHEA replacement studies in humans.