Synergistic Interaction Between Dehydroepiandrosterone and Prednisolone in the Inhibition of Rat Lymphocyte Proliferation

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Abstract
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 the incorporation of 3H-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 between 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 lymphocytes. DHEA with an IC50 value of 13.4 pM was a thousand times less potent than PD which had an IC50 value of 5.4 nM. Synergy was observed between DHEA and PD. The intensity of the interaction appeared to be function of the molar ratio of the two drugs. The association of DHEA and PD could produce enhanced steroid effects in anti-inflammatory therapy.