Holdsworth Stephen R, Gan Poh-Yi
Center for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and Department of Nephrology, Monash Health, Clayton, Victoria, Australia
Center for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and.
Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2243-54. doi: 10.2215/CJN.07590714. Epub 2015 May 4.
Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.
细胞因子在宿主抵御微生物的防御中发挥着重要作用。它们通过诱导保护性局部炎症和全身急性期反应来协调固有免疫。细胞因子在启动、放大、指导、介导和调节适应性免疫方面也很重要。不幸的是，如果发生过度反应或它们参与指导和介导自身免疫，它们也可能导致组织损伤。在这些情况下，细胞因子是潜在的治疗靶点。在过去20年里，我们见证了生物策略的成功开发和临床应用，这些策略针对特定炎症性疾病中的关键细胞因子，其疗效、特异性和毒性特征对传统药物疗法构成挑战。这些疗法正在寻找新的应用，许多新药物显示出前景。不幸的是，这些基于细胞因子的新疗法对肾脏疾病几乎没有效果。这篇综述提供的证据表明，常见的肾脏疾病，包括那些导致急性肾损伤的疾病以及自身免疫性增殖性和新月形肾小球肾炎，具有细胞因子介导特征，这表明它们可能易受针对细胞因子的治疗策略的影响。
