THE EFFECTS OF CYCLOSPORINE-A AND FK506 ON PROLIFERATION AND IL-8 PRODUCTION OF CULTURED HUMAN KERATINOCYTES

The present study was conducted to determine whether cyclosporin A (CsA) and FK506 could be effective in inhibiting the proliferation and cytokine secretion of normal human epidermal keratinocytes (NHEK). NHEK proliferation in the presence of CsA and FK506 at the concentrations 10(-9) to 10(-5) M at 24 and 48 h time points was measured colorimetrically by the MTS assay. CsA had inhibitory effects from 10(-6) to 10(-5) M, while FK506 had no effect, except for toxicity at the very highest concentrations(5 x 10(-6) M and higher). NHEK cells spontaneously secrete IL-8 (243.4 +/- 55.5 pg/ml), and this baseline level was augmented by TNF-alpha alone, or synergistically by TNF-alpha and IFN-gamma, which are thought to be secreted by T cells. Neither CsA nor FK506 had any significant effect on either spontaneous or cytokine-stimulated keratinocyte IL-8 production. Therefore, it is most likely that the two drugs indirectly inhibit the keratinocyte inflammatory response through their actions on T cells or other immunocompetent cells.