Interleukin (IL)‐18 is a pro‐inflammatory cytokine belonging to the IL‐1 family, first identified for its interferon‐γ‐inducing properties. IL‐18 regulates both T helper (Th) 1 and Th2 responses. It acts synergistically with IL‐12 in the Th1 paradigm, whereas with IL‐2 and without IL‐12 it can induce Th2 cytokine production from cluster of differentation (CD)4⁺ T cells, natural killer (NK cells, NKT cells, as well as from Th1 cells. IL‐18 also plays a role in the hemophagocytic lymphohistiocytosis, a life‐threatening condition characterized by a cytokine storm that can be secondary to infections. IL‐18‐mediated inflammation was largely studied in animal models of bacterial, viral, parasitic, and fungal infections. These studies highlight the contribution of either IL‐18 overproduction by the host or overresponsiveness of the host to IL‐18 causing an exaggerated inflammatory burden and leading to tissue injury. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for the coronavirus disease 2019 (COVID‐19). The damage in the later phase of the disease appears to be driven by a cytokine storm, including interleukin IL‐1 family members and secondary cytokines like IL‐6. IL‐18 may participate in this hyperinflammation, as it was previously found to be able to cause injury in the lung tissue of infected animals. IL‐18 blockade has become an appealing therapeutic target and has been tested in some IL‐18‐mediated rheumatic diseases and infantile‐onset macrophage activation syndrome. Given its role in regulating the immune response to infections, IL‐18 blockade might represent a therapeutic option for COVID‐19, although further studies are warranted to investigate more in detail the exact role of IL‐18 in SARS‐CoV‐2 infection.

中文翻译：

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IL-18和感染：靶向疗法有作用吗？

白介素（IL）-18是一种属于IL-1家族的促炎细胞因子，最初因其干扰素-γ的诱导特性而被鉴定。IL-18调节T辅助（Th）1和Th2反应。它在Th1范式中与IL-12协同作用，而在IL-2和没有IL-12的情况下，它可以诱导分化簇（CD）4 ⁺产生Th2细胞因子。IL-18可能参与了这种过度炎症反应，因为以前已经发现它能够在感染动物的肺组织中造成伤害。IL-18阻断已成为有吸引力的治疗目标，并已在某些IL-18介导的风湿性疾病和婴儿发作性巨噬细胞活化综合征中进行了测试。鉴于其在调节对感染的免疫应答中的作用，IL-18阻断可能代表COVID-19的治疗选择，尽管有必要进行进一步的研究以更详细地研究IL-18在SARS-CoV-2感染中的确切作用。IL-18阻滞已成为有吸引力的治疗目标，并已在某些IL-18介导的风湿性疾病和婴儿发作性巨噬细胞活化综合征中进行了测试。鉴于其在调节对感染的免疫应答中的作用，IL-18阻断可能代表COVID-19的治疗选择，尽管有必要进行进一步的研究以更详细地研究IL-18在SARS-CoV-2感染中的确切作用。IL-18阻断已成为有吸引力的治疗目标，并已在某些IL-18介导的风湿性疾病和婴儿发作性巨噬细胞活化综合征中进行了测试。鉴于其在调节对感染的免疫应答中的作用，IL-18阻断可能代表COVID-19的治疗选择，尽管有必要进行进一步的研究以更详细地研究IL-18在SARS-CoV-2感染中的确切作用。