Nagano K, Hori K, Nagane T, Sugawara T, Oh-ishi J, Hayashi H, Watanabe N, Niitsu Y
Pharmaceuticals Laboratory, Asahi Chemical Industry Company, Ltd, Shizuoka, Japan.
Arch Dermatol Res. 1990;282(7):459-62. doi: 10.1007/BF00402623.
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.
在给药4天后,通过组织学方法检查了局部和全身给予肿瘤坏死因子(TNF)对银屑病小鼠尾部模型的影响。以1×10¹至1×10⁴单位/小鼠的剂量皮下注射TNF,导致尾部鳞片中颗粒层呈剂量依赖性形成,其被量化为颗粒层形成延伸超过其表面一半或更多的尾部鳞片的百分比,且大于未处理小鼠和仅接受载体溶液注射的小鼠中出现的百分比。每天以1×10³或1×10⁴单位/小鼠的剂量腹腔注射TNF,持续28天,导致类似的颗粒层形成,并使尾部角质形成细胞的有丝分裂指数显著降低,表明TNF具有抗增殖作用。有丝分裂指数降低和颗粒层的诱导,显然归因于TNF对角质形成细胞增殖和分化的调节,提示TNF可能作为治疗银屑病的药物有效。