IMMUNOMODULATORY EFFECTS OF 3 MACROLIDES, MIDECAMYCIN ACETATE, JOSAMYCIN, AND CLARITHROMYCIN, ON HUMAN T-LYMPHOCYTE FUNCTION IN-VITRO

The effect of three macrolide antibiotics, midecamycin acetate, josamycin, and clarithromycin, on human T-cell function was investigated in vitro. Midecamycin acetate and josamycin suppressed the proliferative response of peripheral blood mononuclear cells stimulated by polyclonal T-cell mitogens at concentrations between 1.6 and 8 mu g/ml. At higher concentrations (40 to 200 mu g/ml), all these drugs showed a marked inhibitory effect. At concentrations of 1.6 to 40 mu g/ml, these drugs suppressed interleukin-2 (IL-2) production induced by mitogen-stimulated T cells, but not the expression of IL-2 receptor (CD25), in a dose-dependent manner. Therefore, the suppressive action on T-lymphocyte proliferation seems to be based on the ability of these drugs to inhibit IL-2 production by T cells. The drugs also inhibited mixed lymphocyte reaction at the same concentrations. Combined treatment with these macrolides and the known immunosuppressants such as FK506 and cyclosporin A resulted in an:increased inhibition of T-cell proliferation. The immunomodulatory properties of the antibiotics may have clinical relevance for modulation of the immune response in transplant patients and in patients with inflammatory diseases.