Several new discoveries have revived interest in the pathogenic potential and possible clinical roles of IL-18. IL-18 is an IL-1 family cytokine with potent ability to induce IFNγ production. However, basic investigations and now clinical observations suggest a more complex picture. Unique aspects of IL-18 biology at the levels of transcription, activation, secretion, neutralization, receptor distribution and signalling help to explain its pleiotropic roles in mucosal and systemic inflammation. Blood biomarker studies reveal a cytokine for which profound elevation, associated with detectable ‘free IL-18’, defines a group of autoinflammatory diseases in which IL-18 dysregulation can be a primary driving feature, the so-called ‘IL-18opathies’. This impressive specificity might accelerate diagnoses and identify patients amenable to therapeutic IL-18 blockade. Pathogenically, human and animal studies identify a preferential activation of CD8⁺ T cells over other IL-18-responsive lymphocytes. IL-18 agonist treatments that leverage the site of production or subversion of endogenous IL-18 inhibition show promise in augmenting immune responses to cancer. Thus, the unique aspects of IL-18 biology are finally beginning to have clinical impact in precision diagnostics, disease monitoring and targeted treatment of inflammatory and malignant diseases.

几项新发现重新唤起了人们对 IL-18 的致病潜力和可能的临床作用的兴趣。IL-18 是一种 IL-1 家族细胞因子，具有诱导 IFNγ 产生的强大能力。然而，基础研究和现在的临床观察表明情况更为复杂。IL-18 在转录、激活、分泌、中和、受体分布和信号传导水平上的生物学独特之处有助于解释其在粘膜和全身炎症中的多效性作用。血液生物标志物研究揭示了一种细胞因子，其显着升高与可检测到的“游离 IL-18”相关，定义了一组自身炎症性疾病，其中 IL-18 失调可能是主要驱动特征，即所谓的“IL-18 病”。这种令人印象深刻的特异性可能会加速诊断并识别出适合治疗性 IL-18 阻断的患者。^{在病理学上，人类和动物研究发现 CD8 +} T 细胞比其他 IL-18 反应性淋巴细胞优先激活。利用产生位点或颠覆内源性 IL-18 抑制作用的 IL-18 激动剂治疗在增强癌症免疫反应方面显示出前景。因此，IL-18生物学的独特之处终于开始在炎症和恶性疾病的精准诊断、疾病监测和靶向治疗方面产生临床影响。