ANTILYMPHOCYTIC ACTIVITY OF ERYTHROMYCIN DISTINCT FROM THAT OF FK506 OR CYCLOSPORINE-A

Erythromycin (EM), a macrolide antibiotic has been recently reported t o depress the extent of inflammation irrespective of its antimicrobial action. Our study was initiated to examine the effect of EM on T cell proliferation in vitro, since other macrolide antibiotics FK506 and r apamycin (RAP) have been well known to possess strong immunosuppressiv e or anti-inflammatory potential. EM had a suppressive effect on the p roliferative response of human lymphocytes stimulated with mitogens an d antigens, while EM had no effect on concanavalin A (Con A)-induced i nterleukin-2 (IL-2) production or IL-2Ralpha (CD25) expression. Delaye d addition of EM after the first 48 hours of mitogenic stimulation did suppress IL-2-dependent proliferation of Con A blasts, whereas pretre atment with EM for the first 48 hours of stimulation did not impede th e subsequent IL-2-dependent proliferation of obtained blast cells. The results indicate that EM suppresses T cell proliferation at a late st age in the activation process by impairing their response to IL-2. Thi s antilymphocytic action of EM was quite distinct from that of FK506 o r cyclosporin A (CsA) but was similar to that of RAP. Unlike RAP, howe ver, EM did not antagonize FK506-induced suppression but potentiated t he action of FK506 and CsA. The addition of an enteric hormone motilin , a receptor of which was previously found to be occupied by EM, unaff ected the lymphocyte proliferation and the subsequent EM-induced suppr ession. These data suggest that EM operates through an undefined mecha nism probably distinct from that of FK506, CsA, RAP or motilin.