Macrophage-Myocyte Cross Talk Induces M1 Polarization and Inflammatory Cytokine Production During Cancer Cachexia.

Cancer cachexia (CC) significantly reduces survival in patients with cancer, and intramuscular inflammation plays an important role in disease progression. Macrophages, as key mediators of the innate immune response, contribute to muscle inflammation by secreting pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), in response to various stimuli. Despite their importance, the mechanisms of macrophage polarization within the cachectic skeletal muscle and the subsequent impacts on muscle inflammation remain poorly understood. In this study, we used a murine model of CC to explore the interaction between macrophages and myocytes during muscle inflammation. Our results demonstrate that cachectic myocytes recruit M1-polarized macrophages that amplify local inflammation via the secretion of IL-1β, IL-6, and TNF-α. These findings underscore the pivotal role of macrophage-derived cytokines in the pathogenesis of cancer-induced muscle inflammation and suggest that targeting macrophage-driven inflammatory pathways may be an effective therapeutic strategy for mitigating muscle wasting in CC.