IL-1β-mediated inflammatory responses in intervertebral disc degeneration: Mechanisms, signaling pathways, and therapeutic potential

Intervertebral disc degeneration (IDD) has been widely recognized as the primary cause of low back pain and is one of the major chronic diseases imposing a severe socioeconomic burden worldwide. IDD is a degenerative process characterized by inflammatory responses, and its underlying pathological mechanisms remain complex. Genetic, developmental, biochemical, and biomechanical factors contribute to the development of IDD. There is a pressing need for an effective non-surgical treatment, mainly due to the lack of comprehensive understanding of the specific mechanisms involved and the effective therapeutic targets for IDD. Recently, interleukin (IL)-1β has been recognized as an essential inflammatory factor and a key mediator of the inflammatory process in IDD. Current studies have found that IL-1β is mainly involved in IDD by affecting the metabolism of the extracellular matrix and regulating cell death (RCD), such as apoptosis, pyroptosis, and ferroptosis (a new form of RCD). Although analysis of clinical samples from different laboratories confirmed how IL-1β is induced in IDD, its specific signal transduction pathway, and the inflammatory role mediated in IDD remains unclear. This review describes the molecules and mechanisms involved in IL-1β-mediated inflammatory responses, and their roles in resolving the inflammatory process in IDD. Understanding the signaling pathways involved in IL-1β may lead to a new class of targets that promote remission for IDD patients. This review aims to provide a framework for the treatment of IDD by analyzing the signaling mechanism and function related to IL-1β, especially in terms of inflammation, matrix metabolism, and cell death regulation.