Mechanisms and clinical research progress of IL-6-mediated crosstalk between the alveolar microenvironment and the immune system in patients with severe pneumonia undergoing mechanical ventilation.

Severe pneumonia is a common critical illness encountered in clinical practice. Although mechanical ventilation is essential for life support, it can paradoxically result in ventilator-induced lung injury and exacerbate pulmonary inflammation. Interleukin-6 (IL-6) is a key pleiotropic cytokine with both proinflammatory and immunometabolic effects, playing a crucial role in regulating the alveolar microenvironment and systemic immune responses in patients with severe pneumonia. Current evidence suggests that IL-6 overexpression is closely associated with increased alveolar inflammation, immune dysregulation, and damage to lung parenchyma. Nevertheless, the dynamic changes of IL-6 during mechanical ventilation and their clinical implications have yet to be fully clarified. This review comprehensive narrative reviewexplores the biological properties of IL-6, its production and regulatory mechanisms during alveolar inflammation in severe pneumonia, the effects of mechanical ventilation on IL-6 levels, IL-6-mediated immune dysregulation and lung injury, its diagnostic and prognostic value as a biomarker, targeted therapeutic strategies against IL-6, and future research directions. By synthesizing recent basic and clinical evidence, this comprehensive narrative review seeks to establish a theoretical foundation for precision medicine and advance the development of individualized immunomodulatory strategies for this patient population.