Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease
Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease
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DOI：
10.1038/nm804
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发表时间：
2003-01-01
期刊：
影响因子：
82.9
通讯作者：
Röcken, M
中科院分区：
文献类型：
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作者：
Ghoreschi, K;Thomas, P;Röcken, M
在实验动物中，选择性地将产生干扰素-γ(IFN-γ)的辅助性T细胞(Th1)向产生白细胞介素4(IL-4)的(Th2)表型倾斜，可以在不引起全身免疫抑制的情况下缓解自身免疫性疾病。在一项前瞻性剂量递增研究中，我们评估了20名严重银屑病患者使用人IL-4(rhuIL-4)的治疗情况。该疗法耐受性良好，在6周内所有患者的临床评分都有所下降，15名患者的病情改善幅度超过68%。RhuIL-4用量在0.2ug~0.5ug时临床评分的稳定下降明显优于rhuIL-40.1ug时(P=0.009)。在银屑病皮损中，0.2-0.5毫克/公斤的rhuIL-4治疗可降低与银屑病直接相关的两种细胞因子IL-8和IL-19的浓度；降低趋化因子受体CCR5(+)Th1细胞的数量；降低干扰素-γ/IL-4的比率。在循环中，0.2-0.5µg/kg rhuIL-4使IL-4(+)CD4(+)T细胞数量增加两到三倍。因此，IL-4治疗可以诱导人类CD4(+)T细胞分化为Th2，有望成为治疗银屑病的潜在药物，银屑病是一种典型的Th1相关自身免疫性疾病。
Selective skewing of autoreactive interferon-gamma (IFN-gamma)-producing T helper cells (Th1) toward an interleukin-4 (IL-4)-producing (Th2) phenotype can in experimental animals alleviate autoimmune disease without inducing general immunosuppression. In a prospective dose escalation study, we assessed treatment with human IL-4 (rhuIL-4) in 20 patients with severe psoriasis. The therapy was well tolerated, and within six weeks all patients showed decreased clinical scores and 15 improved more than 68%. Stable reduction of clinical scores was significantly better at 0.2-0.5 mug rhuIL-4 than at less than or equal to0.1 mug rhuIL-4 (P = 0.009). In psoriatic lesions, treatment with 0.2-0.5 mug/kg rhuIL-4 reduced the concentrations of IL-8 and IL-19, two cytokines directly involved in psoriasis; the number of chemokine receptor CCR5(+) Th1 cells; and the IFN-gamma/IL-4 ratio. In the circulation, 0.2-0.5 mug/kg rhuIL-4 increased the number of IL-4(+)CD4(+) T cells two- to three-fold. Thus, IL-4 therapy can induce Th2 differentiation in human CD4(+) T cells and has promise as a potential treatment for psoriasis, a prototypic Th1-associated autoimmune disease.