SYNERGISTIC INTERACTION BETWEEN DEHYDROEPIANDROSTERONE AND PREDNISOLONE IN THE INHIBITION OF RAT LYMPHOCYTE-PROLIFERATION

The interaction between dehydroepiandrosterone (DHEA) and prednisolone (PD) in the inhibition of rat lymphocyte proliferation was evaluated. The in vitro proliferative response of splenocytes from male Sprague- Dawley rats stimulated with phytohemagglutinin (PHA) was measured by t he incorporation of H-3-thymidine into the DNA. DHEA and PD were added at the initiation of cultures individually and in various molar ratio combinations. The search for synergy, additivity or antagonism betwee n the two compounds was performed by using the median-effect method of Chou and Talalay and Drewinko's statistical analysis. Both compounds individually inhibit the proliferation of PHA-stimulated rat lymphocyt es. DHEA with an IC50 value of 13.4 mu M was a thousand times less pot ent than PD which had an IC50 value of 5.4 nM. Synergy was observed be tween DHEA and PD. The intensity of the interaction appeared to be fun ction of the molar ratio of the two drugs. The association of DHEA and PD could produce enhanced steroid effects in anti-inflammatory therap y.