Diphenylhydantoin inhibits cortisol-induced lysis of thymocytes.

Diphenylhydantoin (DPH) shares two features with cortisol: immunosuppression and cleft palate formation. We tested the hypothesis that DPH would have effects on lymphocytes in vitro similar to those induced by cortisol, and the corollary that DPH would inhibit those cortisol effects. We found that DPH lysed rat thymocytes, although at higher concentrations than cortisol. When combined, DPH inhibited cortisol lysis of thymocytes. Neither drug lysed human phytohemagglutinin (PHA)-stimulated cells, but both drugs depressed DNA and RNA syntheses in PHA cells. DPH augmented cortisol inhibition of DNA and RNA syntheses in PHA cells and DNA synthesis in rat thymocytes. It had no effect on cortisol inhibition of RNA synthesis in rat thymocytes. It appears that DPH has a cortisol-like action (lysis of rat thymocytes). The actions of this drug enable us to show that cortisol lysis and the inhibition of DNA or RNA synthesis can be associated. These phenomena may explain some immunosuppressive effects of DPH in the human.