INHIBITION OF CYTOKINE GENE-EXPRESSION IN MOUSE SKIN BY SUBCUTANEOUS INJECTION OF CYCLOSPORINE

Cyclosporine (CsA) has been shown to be an effective therapeutic agent for a wide variety of cutaneous diseases yet its exact mechanism of a ction is still unclear, although one well-defined effect of CsA is the inhibition of T-cell-derived cytokine expression. We recently demonst rated in vitro that CsA inhibits cell proliferation and suppresses cyt okine gene expression in keratinocytes. In this study, we report the i n vivo effects of CsA on skin cytokine gene expression as determined b y reverse-transcriptase polymerase chain reaction. C57BL6 mice (female , 8-10 weeks old) were subcutaneously injected with CsA in olive oil ( 0, 5 and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited both interleukin (IL)-1 alpha and tumor necrosis factor alpha gene expression by about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6 gene expression did not signific antly change. Injection of 10 mg/kg CsA inhibited expression of all th ree genes by 80-90% relative to control levels. These data show that C sA can inhibit constitutive cytokine gene expression in mouse skin.