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.
Dawson
J
J
Preclinical Reseacrh, Sandoz Pharma AG., Basel, Switzerland. Janet.Dawson@gwa.sandoz.com
Hurtenbach
U
U
MacKenzie
A
A
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine