FK506 and Cyclosporin A Enhance IL-6 Production in Monocytes: A single-Cell Assay

[摘要] The effect of FK506 and cyclosporin A (CsA) on the production ofinterleukin 6 (IL-6) in adherent monocytes was studied at asingle-cell level by the avidinbiotin- peroxidase complex methods.The percentage of IL-6-producing monocytes increased when stimulatedwith lipopolysaccharide (LPS) at concentrations between 10 ng/ml and10 μg/ml, in a dose dependent manner. Both FK506 and CsAenhanced the percentage of IL-6- producing monocytes stimulated with100 pg/ml-1 μg/ml of LPS up to values near thoseobtained with 10 μg/ml of LPS. The enhancement by FK506 andCsA was not seen when monocytes were stimulated with a highconcentration of LPS (10 μg/ml). When monocytes werestimulated with a low concentration of LPS (10 ng/ml), FK506 andCsA enhanced IL-6 production in a dose dependent manner, at a drugconcentration of 0.12 nM–1.2 μM (0.1–1 000 ng/ml)for FK506 and 0.83 nM–8.3 μM (1–10 000 ng/ml) forCsA. The optimal effect of FK506 was achieved at a concentration7-fold lower than that of CsA. In contrast, production of turnoutnecrosis factor-α (TNFα and interleukin 1β(IL-1β) was slightly suppressed by FK506 and CsA at theconcentrations tested. Moreover, pretreatment of monocytes withFK506 and CsA had a significant enhancing effect on LPS-induced IL-6production, while treatment with FK506 or CsA after LPS stimulationhad no effects on IL-6 production, suggesting that the enhancingeffect of each drug is exerted before LPS stimulation or at an earlystage of the post-receptor pathway after LPS stimulation. Theseexperiments demonstrate that FK506 and CsA can selectively enhanceIL-6 production in monocytes under certain conditionsinvitroand, possibly, alsoin vivo.

[学科分类] 生理学与病理学