Abstract
Pneumonia remains a major global health challenge, necessitating the development of effective therapeutic approaches. Recently, necroptosis, a regulated form of cell death, has garnered attention in the fields of pharmacology and immunology for its role in the pathogenesis of pneumonia. Characterized by cell death and inflammatory responses, necroptosis is a key mechanism contributing to tissue damage and immune dysregulation in various diseases, including pneumonia. This review comprehensively analyzes the role of necroptosis in pneumonia and explores potential pharmacological interventions targeting this cell death pathway. Moreover, we highlight the intricate interplay between necroptosis and immune responses in pneumonia, revealing a bidirectional relationship between necrotic cell death and inflammatory signaling. Importantly, we assess current therapeutic strategies modulating necroptosis, encompassing synthetic inhibitors, natural products, and other drugs targeting key components of the programmed necrosis pathway. The article also discusses challenges and future directions in targeting programmed necrosis for pneumonia treatment, proposing novel therapeutic strategies that combine antibiotics with necroptosis inhibitors. This review underscores the importance of understanding necroptosis in pneumonia and highlights the potential of pharmacological interventions to mitigate tissue damage and restore immune homeostasis in this devastating respiratory infection.