In vivo introduction of the interleukin-6 gene into keratinocytes

To understand biological function of interleukin-6 (IL-6) in the skin in vi vo, we constructed a vector which strongly expressed human IL-6 in keratino cytes and introduced it into rat keratinocytes in vivo by the naked DNA met hod. The overexpression of IL-6-induced macroscopic erythema and histologic ally evident keratinocyte proliferation and lymphocytic infiltration in the treated area of rat skin. Since previous studies using IL-6 transgenic mic e have not shown skin inflammation of these mice, our results first provide direct evidence that IL-6 is responsible for the development of inflammato ry skin diseases. We then introduced and expressed the IL-6 mutant genes, w hich were designed to behave as IL-6R alpha antagonists, and found that the ir ability to induce erythema was lower than that of the wild-type gene. Fu rthermore, preintroduction of some mutant genes inhibited the erythema indu ced by postintroduction of the wild-type IL-6 gene, suggesting that the mut ant forms of IL-6 prevent wild-type IL-6 from binding to IL-6R alpha. These results indicate that keratinocyte gene therapy may be possible for inflam matory skin diseases using IL-6 mutant genes.