Keicho N, Sawada S, Kitamura K, Yotsumoto H, Takaku F
Third Department of Internal Medicine, University of Tokyo, Japan.
Cell Immunol. 1991 Feb;132(2):285-94. doi: 10.1016/0008-8749(91)90028-a.
A recently discovered immunosuppressive agent, FK506, has been shown to be effective primarily as an inhibitor of T cell responses in vitro, but little is known about its effects on accessory cell function. This study was undertaken to determine the effect of FK506 on interleukin 1 (IL-1) production by macrophages, by using a sensitive and specific enzyme-linked immunosorbent assay. FK506 partially suppressed IL-1 alpha release, from macrophage-like U937 cells stimulated with phorbol myristate acetate and from human monocytes and alveolar macrophages activated with lipopolysaccharide, in a dose-dependent manner. Moreover, it was indicated that FK506 suppressed not only IL-1 release but also IL-1 synthesis itself, by measurement of cell-associated IL-1 alpha of U937 cells. The optimal concentrations of FK506 for suppressing IL-1 alpha did not affect cell viability or proliferation, and were 10- to 100-fold lower than those of cyclosporin A. It is concluded that FK506 affects macrophage physiology, suppressing IL-1 alpha production significantly. Thus, FK506 has the potency to act on non-T cells and the effect on macrophages may play an additional role in preventing graft rejection.
一种最近发现的免疫抑制剂FK506，已被证明在体外主要作为T细胞反应的抑制剂有效，但对其对辅助细胞功能的影响知之甚少。本研究旨在通过使用灵敏且特异的酶联免疫吸附测定法来确定FK506对巨噬细胞产生白细胞介素1（IL-1）的影响。FK506以剂量依赖的方式部分抑制了佛波酯肉豆蔻酸酯刺激的巨噬细胞样U937细胞、脂多糖激活的人单核细胞和肺泡巨噬细胞释放的IL-1α。此外，通过测量U937细胞的细胞相关IL-1α表明，FK506不仅抑制IL-1释放，还抑制IL-1合成本身。抑制IL-1α的FK506的最佳浓度不影响细胞活力或增殖，且比环孢素A的浓度低10至100倍。得出的结论是，FK506影响巨噬细胞生理学，显著抑制IL-1α的产生。因此，FK506有作用于非T细胞的潜力，并且对巨噬细胞的作用可能在预防移植排斥中发挥额外作用。
