EFFECT OF PHARMACOLOGICAL AGENTS ON THE PRODUCTION OF INTERLEUKIN-10 BY THE MURINE D10.G4.1 T(H)2 CELL-LINE IN-VITRO

It is becoming increasingly clear that the clinical courses of a varie ty of autoimmune and infectious diseases are influenced by the balance of T(H)1 and T(H)2 cell subsets that are generated during the immune response. IL-10 is one of several cytokines which influences the diffe rentiation of T-H cell subsets and represents a target For therapeutic intervention. We have evaluated a variety of pharmacological agents f or their ability to modulate IL-10 release by the murine D10.G4.1 T(H) 2 cell line when stimulated with concanavalin-A in the presence of IL- 1 alpha. Several were inhibitory, and the concentrations which caused a 50% reduction in IL-10 production were 0.38 mu M cyclosporin-A, 0.00 73 mu M dexamethasone, 0.045 mu M prednisolone and 0.31 mu M cyclohexi mide. Methotrexate and pentoxifylline caused a weak but statistically significant reduction in IL-10 production at a concentration of 10 mu M (P less than or equal to 0.05), whereas amrinone and azathioprine ha d no clear effect. The pharmacological agents tested are known to exer t multiple effects and were evaluated with a view to their use as refe rence standards in an ongoing screening programme to identify novel co mpounds which specifically modulate IL-10 production.