Reynolds N J, Al-Daraji W I
Department of Dermatology, Medical School, University of Newcastle upon Tyne, UK.
Clin Exp Dermatol. 2002 Oct;27(7):555-61. doi: 10.1046/j.1365-2230.2002.01148.x.
Controlled trials and clinical experience indicate that systemic cyclosporin A and tacrolimus are effective treatments for psoriasis, and that cyclosporin A also improves atopic eczema. A variety of other inflammatory and non-inflammatory skin diseases are probably also responsive to these drugs. However, the widespread and longer-term use of cyclosporin A and tacrolimus are limited by side effects. The molecular mechanisms of action of cyclosporin A, tacrolimus and a related drug, sirolimus, have been well defined in T cells and involve inhibition of critical signalling pathways that regulate T cell activation. For example cyclosporin and tacrolimus inhibit calcineurin phosphatase activity and thereby inhibit activation of the transcription factor NFAT. The therapeutic efficacy of topical calcineurin inhibitors in atopic eczema have restimulated interest in the mechanism of action of these drugs in skin disease. Recently the expression pattern of calcineurin and NFAT has been defined in non-immune tissues including the akin. The relevance of this to the mechanism of action of systemic and topical calcineurin inhibitors and sirolimus in skin disorders is discussed.
对照试验和临床经验表明，全身性环孢素A和他克莫司是治疗银屑病的有效药物，环孢素A还可改善特应性皮炎。多种其他炎性和非炎性皮肤病可能对这些药物也有反应。然而，环孢素A和他克莫司的广泛及长期使用受到副作用的限制。环孢素A、他克莫司及一种相关药物西罗莫司在T细胞中的分子作用机制已得到明确界定，涉及抑制调节T细胞活化的关键信号通路。例如，环孢素和他克莫司抑制钙调神经磷酸酶的磷酸酶活性，从而抑制转录因子NFAT的活化。局部应用钙调神经磷酸酶抑制剂治疗特应性皮炎的疗效重新激发了人们对这些药物在皮肤病作用机制的兴趣。最近，钙调神经磷酸酶和NFAT在包括皮肤在内的非免疫组织中的表达模式已得到明确。本文讨论了这与全身性和局部性钙调神经磷酸酶抑制剂及西罗莫司在皮肤疾病作用机制的相关性。
