Niewold Timothy B, Lehman Julia S, Gunnarsson Iva, Meves Alexander, Oke Vilija
Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, New York, NY, United States.
Department of Dermatology, Mayo Clinic, Rochester, MN, United States.
Front Immunol. 2025 Jun 2;16:1524026. doi: 10.3389/fimmu.2025.1524026. eCollection 2025.
Interleukin (IL)-16 is expressed mostly by the cells of the human immune system. Upon cell activation IL-16 is cleaved, forming two functional proteins, one regulating cell cycle and the other acting as chemoattractant for the cells carrying CD4 or CD9. Increased levels of IL-16 are found in the circulation and at the sites of inflammation, infection and cancer. Polymorphisms in the IL-16 gene have been coupled to several of these conditions and high IL-16 has been suggested as a disease biomarker. Using unbiased proteomic approach we and others independently identified IL-16 as a biomarker of severe lupus nephritis, and top-expressed cytokine in skin lesions of lupus erythematosus. Recently, an unbiased investigation identified IL-16 as a top candidate for novel drug target. Blockade of IL-16 showed positive therapeutic effects in several animal models of human disease with low rate of side effects. Importantly, it has been recently demonstrated that IL-16 can be released during pyroptosis, a proinflammatory cell death pathway. This finding disclosed a novel role of IL-16 as a mediator of response to the proinflammatory cell death and may explain why IL-16 is detected at the sites of inflammation, infection or cancer. In this review we cover the knowledge on the biology of IL-16 and its importance in human diseases. We aim that this manuscript will be informative and prove benefits of possible therapeutic blockade of IL-16.
白细胞介素（IL）-16主要由人类免疫系统的细胞表达。细胞激活后，IL-16被切割，形成两种功能蛋白，一种调节细胞周期，另一种作为携带CD4或CD9细胞的趋化因子。在循环系统以及炎症、感染和癌症部位发现IL-16水平升高。IL-16基因的多态性与其中几种情况相关，高IL-16已被认为是一种疾病生物标志物。我们和其他人通过无偏蛋白质组学方法独立鉴定出IL-16是重症狼疮性肾炎的生物标志物，也是红斑狼疮皮肤病变中表达最高的细胞因子。最近，一项无偏研究确定IL-16是新型药物靶点的顶级候选物。阻断IL-16在几种人类疾病动物模型中显示出积极的治疗效果，且副作用发生率低。重要的是，最近已证明IL-16可在焦亡（一种促炎细胞死亡途径）过程中释放。这一发现揭示了IL-16作为促炎细胞死亡反应介质的新作用，并可能解释了为什么在炎症、感染或癌症部位能检测到IL-16。在本综述中，我们涵盖了关于IL-16生物学及其在人类疾病中的重要性的知识。我们旨在使本文具有参考价值，并证明对IL-16进行可能的治疗性阻断的益处。
