The discovery of interleukin (IL)-6 and its receptor subunits provided a foundation to understand the biology of a group of related cytokines: IL-12, IL-23, and IL-27. These family members utilize shared receptors and cytokine subunits and influence the outcome of cancer, infection, and inflammatory diseases. Consequently, many facets of their biology are being therapeutically targeted. Here, we review the landmark discoveries in this field, the combinatorial biology inherent to this family, and how patient datasets have underscored the critical role of these pathways in human disease. We present significant knowledge gaps, including how similar signals from these cytokines can mediate distinct outcomes, and discuss how a better understanding of the biology of the IL-12 family provides new therapeutic opportunities.

白细胞介素 (IL)-6 及其受体亚基的发现为了解一组相关细胞因子（IL-12、IL-23 和 IL-27）的生物学奠定了基础。这些家族成员利用共享的受体和细胞因子亚基，影响癌症、感染和炎症性疾病的结果。因此，它们生物学的许多方面都成为治疗的目标。在这里，我们回顾了该领域的里程碑式发现、该家族固有的组合生物学，以及患者数据集如何强调这些途径在人类疾病中的关键作用。我们提出了重大的知识差距，包括这些细胞因子的相似信号如何介导不同的结果，并讨论了更好地了解 IL-12 家族的生物学如何提供新的治疗机会。