Cyclosporin A inhibits the in vivo production of interleukin-1beta and tumour necrosis factor alpha, but not interleukin-6, by a T-cell-independent mechanism.

The effect of cyclosporin A (CsA) on cytokine production in the tissue chamber model of acute inflammation was investigated. CsA caused a dose-related inhibition of interleukin 1beta(IL-1beta) production in both normal and athymic mice, confirming earlier conclusions that this effect is not T cell dependent (ED50s 40 and 53 mg/kg p.o., respectively). Tumour necrosis factor alpha (TNF-alpha) levels were similarly affected with ED50s of 40 and 58 mg/kg p.o. for normal and athymic mice, respectively. By contrast, CsA inhibited interleukin 6 (IL-6) production only in normal mice (ED50 27 mg/kg p.o.) Differences in the absolute production of the three cytokines in normal and athymic mice were also noted. IL-1beta and IL-6 levels were two-fold higher in athymic mice, while for TNF-alpha, there was no difference between the two groups. The present findings support the authors' original hypothesis, that the inhibitory mechanism of CsA on IL-1beta is not mediated via T cells. The same mechanism also seems responsible for the inhibition of TNF-alpha production, but not for IL-6, where inhibition by CsA appears to require the presence of T cells.