Effect of tumour necrosis factor in the mouse-tail model of psoriasis

The effects of local and systemic administration of tumour necrosis factor (TNF) on the mouse-tail model of psoriasis were examined histologically at 4 days after administration. Subcutaneous injection of TNF at 1 x 10(1) to 1 x 10(4) units/mouse resulted in dose-dependent formation of a granular layer in the tail scales, which was quantified as the percentage of tail scales having granular layer formations extending over half or more of their surface and was larger than that occurring in untreated mice and in mice receiving injections of vehicle solution alone. Daily intraperitoneal injection of TNF at 1 x 10(3) or 1 x 10(4) units/mouse for 28 days resulted in similar granular layer formation and in a significantly reduced mitotic index of the tail keratinocytes, indicating an antiproliferative effect of TNF. The lowered mitotic index and the induction of granular layers, apparently attributable to a modulation of keratinocyte proliferation and differentiation by TNF, suggest that TNF may be effective as a drug for treatment of psoriasis.