Growth Differentiation Factor-15 Orchestrates Inflammation-Related Diseases via Macrophage Polarization

Macrophage polarization is a critical determinant of disease progression and regression. Studies on macrophage plasticity and polarization can provide a theoretical basis for the tactics of diagnosis and treatment for macrophage-related diseases. These include inflammation-related diseases, such as sepsis, tumors, and metabolic disorders. Growth differentiation factor-15 (GDF-15) or macrophage inhibitory cytokine-1, a 25 kDa secreted homodimeric protein, is a member of the transforming growth factor-β (TGF-β) superfamily that is released in response to external stressors. GDF-15 regulates biological effects such as tumor occurrence, inflammatory response, tissue damage, angiogenesis, and bone metabolism. It has been shown to exert anti-inflammatory and pro-inflammatory effects in inflammation-related diseases. Moreover, inflammatory stimuli can induce GDF-15 expression in immune and parenchymal cells. GDF-15 exhibits a feedback inhibitory effect by inhibiting tumor necrosis factor-α secretion during the macrophage activation anaphase, suggesting that there may be a close association between the two. GDF-15 directly induces CD14