Keicho N, Kudoh S, Yotsumoto H, Akagawa K S
Department of Immunology, National Institute of Health, Tokyo, Japan.
J Antibiot (Tokyo). 1993 Sep;46(9):1406-13. doi: 10.7164/antibiotics.46.1406.
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.
红霉素（EM）是一种大环内酯类抗生素，最近有报道称，无论其抗菌作用如何，它都能减轻炎症程度。由于其他大环内酯类抗生素FK506和雷帕霉素（RAP）具有很强的免疫抑制或抗炎潜力，我们开展了这项研究，以检测EM对体外T细胞增殖的影响。EM对由丝裂原和抗原刺激的人淋巴细胞增殖反应具有抑制作用，而EM对刀豆蛋白A（Con A）诱导的白细胞介素-2（IL-2）产生或IL-2Rα（CD25）表达没有影响。在丝裂原刺激的最初48小时后延迟添加EM确实会抑制Con A母细胞的IL-2依赖性增殖，而在刺激的最初48小时用EM预处理并不会阻碍随后获得的母细胞的IL-2依赖性增殖。结果表明，EM通过损害T细胞对IL-2的反应，在激活过程的后期抑制T细胞增殖。EM的这种抗淋巴细胞作用与FK506或环孢素A（CsA）的作用截然不同，但与RAP的作用相似。然而，与RAP不同的是，EM不会拮抗FK506诱导的抑制作用，反而会增强FK506和CsA的作用。添加一种肠激素胃动素（其受体先前被发现可被EM占据）对淋巴细胞增殖及随后的EM诱导的抑制作用没有影响。这些数据表明，EM通过一种可能不同于FK506、CsA、RAP或胃动素的未知机制发挥作用。
