J.Jpn. Surg. Soc.. 91(8): 1011-1015, 1990

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Original article

THE EFFECT OF COMBINATION THERAPY OF CYCLOSPORINE WITH STEROID ON THE PRODUCTION OF γ-INTERFERON AND INTERLEUKIN-1 IN KIDNEY TRANSPLANT RECIPIENTS

The present study examined the effects of CsA administered with steroid in vivo on the capacity of kidney transplant recipient mononuclear cells to generate cytokines and their gene expression at the level of messenger RNA (mRNA). Peripheral blood mononuclear cells (PBMC) from CsA-Prednisolon(Pred) treated recipients displayed 66.9% inhibition (54.3+12.4IU/ml, n=42, p＜0.01) of γ-IFN production compared with normal individuals (134.6+18.6IU/ml, n=23). Azathioprine(Az)-Pred treated recipients displayed significantly less inhibition of γ-INF generation (96.0+16.1IU/ml, n=22, p＜0.05) than CsA treated patients. Macrophages (mφ) from CsA-Pred treated recipients displayed 60.0% inhibition (5.1+0.7U/ml, n=20, p＜21). These result were confirmed by the experiments using cDNA probe for γ-IFN or IL-1 (α, β). High levels of γ-IFN mRNA in PHA-stimulated PBL or IL-1 (β) mRNA in LPS-stimulated mφwere present in normal individuals, but not in CsA treated recipients as judged by hybridization to acloned human γ-IFN or IL-1 (β) cDNA probe. These studies demonstrated that combination therapy of CsA with steroid inhibits both γ-IFN and IL-1 gene expression at the level of mRNA at physiological concentration.

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