Li Xinxin, Huang Chen, Rai Kul Raj, Xu Quanming
Meizhouwan Vocational Technology College, Putian, China.
Scientific Research and Experiment Center, Fujian Police College, Fuzhou, China.
Front Cell Infect Microbiol. 2025 Jul 7;15:1605446. doi: 10.3389/fcimb.2025.1605446. eCollection 2025.
Interleukin-6 (IL-6), a pleiotropic cytokine, is induced by infection of influenza A virus (IAV), where it plays a pivotal role in immune defense and the regulation of inflammation. IAV induces IL-6 transcription upon recognition by pattern recognition receptors, which activate downstream signaling cascades, leading to the activation of transcription factors. Activated transcription factors subsequently regulate the expression of IL-6 in innate immune cells, such as macrophages, dendritic cells, and epithelial cells. IL-6 contributes to antiviral immunity by promoting the recruitment of immune cells to sites of infection and amplifying the inflammatory response. While optimal IL-6 production is essential for effective anti-IAV immunity, excessive IL-6 production can contribute to a dysregulated immune response, leading to a cytokine storm. In this context, IL-6 signaling, in coordination with other proinflammatory cytokines such as TNF-α and IL-1β, not only enhances its own production but can also serve as a key mediator of inflammation. This cascade can result in exaggerated immune responses, causing tissue damage and potentially leading to severe outcomes, including organ failure and death. Understanding the molecular mechanisms underlying cytokine storms presents important therapeutic opportunities. However, the precise pathways responsible for excessive IL-6 production and its dysregulation during IAV infection is not fully understood. This review explores the reported mechanisms regulating IL-6 induction in response to IAV and its innate immune role in IAV pathogenesis, highlighting existing research gaps in understanding IAV-induced IL-6 production and its impact on immune modulation. A deeper understanding of IAV-induced IL-6 production and signaling could inform the development of targeted therapies to more effectively manage influenza.
白细胞介素-6（IL-6）是一种多效性细胞因子，由甲型流感病毒（IAV）感染诱导产生，在免疫防御和炎症调节中起关键作用。IAV被模式识别受体识别后诱导IL-6转录，激活下游信号级联反应，导致转录因子活化。活化的转录因子随后调节IL-6在先天免疫细胞（如巨噬细胞、树突状细胞和上皮细胞）中的表达。IL-6通过促进免疫细胞募集到感染部位并放大炎症反应，有助于抗病毒免疫。虽然最佳的IL-6产生对于有效的抗IAV免疫至关重要，但过量的IL-6产生会导致免疫反应失调，引发细胞因子风暴。在这种情况下，IL-6信号与其他促炎细胞因子（如TNF-α和IL-1β）协同作用，不仅增强自身产生，还可作为炎症的关键介质。这种级联反应可导致过度的免疫反应，造成组织损伤，并可能导致严重后果，包括器官衰竭和死亡。了解细胞因子风暴背后的分子机制具有重要的治疗意义。然而，IAV感染期间导致IL-6过量产生及其失调的确切途径尚未完全明确。本综述探讨了已报道的调节对IAV应答诱导IL-6的机制及其在IAV发病机制中的先天免疫作用，强调了在理解IAV诱导的IL-6产生及其对免疫调节影响方面存在的研究空白。对IAV诱导的IL-6产生和信号传导的更深入理解可为开发更有效地管理流感的靶向疗法提供依据。
