Combination therapy of cyclosporine with steroid inhibits ?-interferon and interleukin-1 gene expression at the level of mRNA synthesisin vivo

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Abstract
The present study examined the effect of cyclosporine (CsA) administered with steroidin vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to generate cytokines and their gene expression at the level of messenger RNA (mRNA). PBMC from CsA-prednisolone (Pred)-treated recipients displayed 66.9% inhibition (54.3±12.4 IU/ml;N=42;PN=23). Azathioprine (Az)-Pred-treated recipients displayed significantly less inhibition of γ-IFN generation (96.0±16.1 IU/ml;N=22;PN=20;PN=21). These results were confirmed by the experiments using cDNA probe for γ-IFN or IL-1 (α, β). High levels of γ-IFN mRNA in phytohemagglutinin (PHA)-stimulated PBMC or IL-1(β) mRNA in lipopolysaccharide (LPS)-stimulated mφ were present in normal individuals but not in CsA-treated recipients as judged by hybridization to a cloned 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 concentrations.