Antilymphocytic activity of erythromycin distinct from that of FK506 or cyclosporin A.
Erythromycin (EM), a macrolide antibiotic has been recently reported to 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 rapamycin (RAP) have been well known to possess strong immunosuppressive or anti-inflammatory potential. EM had a suppressive effect on the proliferative response of human lymphocytes stimulated with mitogens and antigens, while EM had no effect on concanavalin A (Con A)-induced interleukin-2 (IL-2) production or IL-2R alpha (CD25) expression. Delayed addition of EM after the first 48 hours of mitogenic stimulation did suppress IL-2-dependent proliferation of Con A blasts, whereas pretreatment with EM for the first 48 hours of stimulation did not impede the subsequent IL-2-dependent proliferation of obtained blast cells. The results indicate that EM suppresses T cell proliferation at a late stage in the activation process by impairing their response to IL-2. This antilymphocytic action of EM was quite distinct from that of FK506 or cyclosporin A (CsA) but was similar to that of RAP. Unlike RAP, however, EM did not antagonize FK506-induced suppression but potentiated the action of FK506 and CsA. The addition of an enteric hormone motilin, a receptor of which was previously found to be occupied by EM, unaffected the lymphocyte proliferation and the subsequent EM-induced suppression. These data suggest that EM operates through an undefined mechanism probably distinct from that of FK506, CsA, RAP or motilin.
Keicho
N
N
Department of Immunology, National Institute of Health, Tokyo, Japan.
Kudoh
S
S
Yotsumoto
H
H
Akagawa
K S
KS
D000941:Antigens / Q000276:immunology; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004357:Drug Synergism; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009037:Motilin / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000941:Antigens; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D009037:Motilin; D004917:Erythromycin; D016572:Cyclosporine; D016559:Tacrolimus