Interferon-β therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production
Interferon-β therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production
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DOI：
10.1002/ana.10084
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发表时间：
2002-02-01
影响因子：
11.2
通讯作者：
Karp, CL
中科院分区：
文献类型：
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作者：
Byrnes, AA;McArthur, JC;Karp, CL
白细胞介素-12在多种动物实验性自身免疫性脑脊髓炎发病机制中的作用白细胞介素-10是白细胞介素-12的主要内源性抑制剂，在这些多发性硬化症的实验替代品中具有很大的保护作用。这些数据表明，白细胞介素-12/白细胞介素-10免疫调节回路是实验性自身免疫性脑脊髓炎疾病表达的关键决定因素。对于多发性硬化症本身，已经报道了相容的细胞因子数据。β干扰素对多发性硬化症有益作用的机制尚不清楚，阻碍了对更有效疗法的研究。值得注意的是，干扰素-β在体外对这些细胞因子具有相互作用，抑制白细胞介素-12并增加白细胞介素-10的产生。为了研究干扰素β对多发性硬化患者白细胞介素-12/白细胞介素-10轴的影响，我们对开始用干扰素β治疗的患者外周血单核细胞产生这些细胞因子进行了表征。治疗前，多发性硬化患者表现出增加刺激白细胞介素-12的生产相比，对照组。干扰素β治疗可抑制白细胞介素-12和增加白细胞介素-10的产生，显著提高分泌的白细胞介素-10与白细胞介素-12的比例：在复发-缓解和进展性疾病患者中同样观察到这些作用，表明干扰素β以被认为对多发性硬化患者有益的方式影响白细胞介素-12/白细胞介素-10轴。可能需要对这些途径进行更特异性的治疗靶向。
Interleukin-12 is critical to the pathogenesis of experimental autoimmune encephalomyelitis in multiple species. Interleukin-10, a dominant endogenous inhibitor of interleukin-12, is largely protective in these, experimental surrogates for multiple sclerosis. Such data have suggested that an interleukin-12/interleukin-10 immunoregulatory circuit is a key determinant of disease expression in experimental autoimmune encephalomyelitis. For multiple sclerosis itself, compatible cytokine data have been reported. The mechanisms underlying the beneficial effects of interferon-beta in multiple sclerosis remain unclear, hampering the search for more effective therapies. Of note, interferon-beta has reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and augmenting interleukin-10 production. To examine the effects of interferon-beta on the interleukin-12/interleukin-10 axis in multiple sclerosis, we characterized the production of these cytokines by peripheral blood mononuclear cells from patients beginning therapy with interferon-beta. Before therapy, multiple sclerosis patients exhibited increased stimulatable interleukin-12 production compared with controls. Interferon-beta therapy leads to inhibition of interleukin-12 and augmentation of interleukin-10 production, significantly elevating the ratio of secreted interleukin-10 to interleukin-12: These effects, observed equally inpatients with relapsing-remitting and progressive disease, indicate that interferon-beta affects the interleukin-12/interleukin-10 axis in ways thought to be beneficial to multiple sclerosis patients. More specific therapeutic targeting of these pathways may be warranted.