Vol. 285, Issue 2, 915-919, May 1998

IL-10 Synergizes with Dexamethasone in Inhibiting Human T Cell Proliferation¹

Mauro Brunetti , Antonella Colasante , Nicola Mascetra, Mauro Piantelli, Piero Musiani and Francesca B. Aiello

Department of Human Pathology (M.B., A.C., M.P., P.M., F.B.A.), "G. D'Annunzio" University, Chieti, Italy and Laboratory of Immunopathology (M.B., A.C., N.M., P.M., F.B.A.), Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy

We have evaluated the effects of dexamethasone (Dex) alone or in combination with interleukin (IL)-10 or transforming growth factor-1 (TGF-1) on human T cell proliferation. Both IL-10 and TGF-1 significantly decreased the Dex concentration needed to inhibit T cell proliferation by 50% (IC₅₀). Dex in combination with IL-10 completely inhibited T cell proliferation, even when IL-10 alone was ineffective, as in the case of phytohemagglutinin-induced T cell proliferation. The evaluation of the results according to the isobole method displayed a potent synergistic activity between Dex and IL-10, whereas the combination of Dex with TGF-1 was additive. IL-10, but not TGF-1, enhanced the inhibitory effect of Dex on IL-2 production. IL-2 and IL-4 only partly antagonized the antiproliferative effect of the combinations. IL-4 was as effective as IL-2 in antagonizing the combination of Dex with TGF-1, but significantly less effective against the combination of Dex with IL-10. IL-10 and TGF-1 are thus able to potentiate the Dex inhibitory effect on T cell proliferation and could be regarded as potential agents for future immunosuppressive protocols.