Cytotoxic and immunologic effects of methotrexate in psoriasis.
Cytotoxic and immunologic effects of methotrexate in psoriasis.
复制标题
甲氨蝶呤对银屑病的细胞毒性和免疫作用。
DOI：
10.1111/1523-1747.ep12505777
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
McCullough,JL
中科院分区：
文献类型：
--
作者：
Weinstein,GD;Jeffes,E;McCullough,JL
根据近期免疫抑制药物环孢素 A 对银屑病有显着改善作用的经验，对甲氨蝶呤 (MTX) 可能的免疫调节活性进行了审查，以寻找 MTX 在银屑病中作用的替代机制。一般认为MTX治疗银屑病的效果与通过抑制DNA合成直接作用于表皮细胞增生有关。现在文献中的几项研究表明，MTX 对银屑病患者以及可能与银屑病具有某些致病相似性的动物模型的免疫系统可能产生影响。在接受 MTX 的银屑病患者中，中性粒细胞的趋化性受到抑制，导致病变皮肤中常见的中性粒细胞的潜在病理活性可能发生改变。 MTX 确实可以改善银屑病和类风湿关节炎。使用佐剂关节炎和移植物抗宿主病 (GVHD) 对后者进行的动物研究表明，MTX 影响这些过程的几种可能机制。在 GVHD 中，MTX 选择性破坏循环 CD8+ 细胞，在佐剂关节炎中，通过抑制 T 细胞功能来阻止巨噬细胞的活化。虽然 MTX 通常尚未在临床上用作免疫相关疾病的免疫调节药物，但它可能具有针对某些疾病的选择性作用。 MTX 和环孢素 A 的作用机制相似，但激活 T 细胞和巨噬细胞的步骤不同。 MTX 对表皮细胞增殖的主要直接作用可能是通过对受影响皮肤中的细胞混合物和全身免疫反应的微妙免疫调节作用来补充甚至介导的。
Based on recent experience that Cyclosporin A, an immunosuppressive drug, produces marked improvement in psoriasis, possible immunomodulatory activities of methotrexate (MTX) have been reviewed to look for alternate mechanisms of MTX action in psoriasis. It is generally considered that the therapeutic results of MTX in psoriasis are related to a direct effect on epidermal cell hyperplasia through inhibition of DNA synthesis. Several studies in the literature now suggest possible effects of MTX on the immune system of psoriatics as well as in animal models that may have some pathogenic similarities to psoriasis. In psoriatics receiving MTX, neutrophil chemotaxis is suppressed, resulting in a possible alteration in the potential pathologic activity of neutrophils commonly found in lesional skin. MTX does improve both psoriatic and rheumatoid arthritis. Animal studies of the latter using adjuvant arthritis and graft vs host disease (GVHD) have indicated several possible mechanisms for MTX that affect these processes. In GVHD, MTX selectively destroys cycling CD8+ cells, and in adjuvant arthritis the activation of macrophages is prevented by inhibition of T-cell function. While MTX generally has not been clinically utilized as an immunomodulatory drug for immunologically related diseases, it may, nonetheless, have selective actions that could be specific for some diseases. MTX and Cyclosporin A could work mechanistically in similar ways but at different steps in the activation of T cells and macrophages. It may be that the major direct effect of MTX on epidermal cell proliferation is complemented or even mediated by subtle immunoregulatory effects on the melange of cells in the affected skin and the systemic immune response.