The article "The M1 and M2 paradigm of macrophage activation: time for reassessment" by Fernando O. Martinez and Siamon Gordon discusses the evolving understanding of macrophage activation and the limitations of the traditional M1/M2 paradigm. Macrophages, key players in the immune system, can be activated through various stimuli, leading to specialized functional phenotypes. The M1/M2 model, initially based on Th1 and Th2 cell responses, has been widely used to categorize macrophage activation, but recent research suggests the need for a more nuanced approach. The M1 phenotype, associated with pro-inflammatory responses, is typically induced by IFN-γ and LPS, while the M2 phenotype, linked to anti-inflammatory and tissue repair functions, is influenced by IL-4, IL-10, and glucocorticoids. However, the article highlights that the M1/M2 model oversimplifies the complex and dynamic nature of macrophage activation, which involves a range of stimuli and signaling pathways. The authors argue that macrophages do not form stable subsets but respond to a combination of factors in their environment. They emphasize the need for a more comprehensive understanding of macrophage activation, considering the interplay of various signals and the context in which they occur. The article concludes that the M1/M2 paradigm, while useful, requires reassessment to better reflect the complexity of macrophage functions in health and disease.The article "The M1 and M2 paradigm of macrophage activation: time for reassessment" by Fernando O. Martinez and Siamon Gordon discusses the evolving understanding of macrophage activation and the limitations of the traditional M1/M2 paradigm. Macrophages, key players in the immune system, can be activated through various stimuli, leading to specialized functional phenotypes. The M1/M2 model, initially based on Th1 and Th2 cell responses, has been widely used to categorize macrophage activation, but recent research suggests the need for a more nuanced approach. The M1 phenotype, associated with pro-inflammatory responses, is typically induced by IFN-γ and LPS, while the M2 phenotype, linked to anti-inflammatory and tissue repair functions, is influenced by IL-4, IL-10, and glucocorticoids. However, the article highlights that the M1/M2 model oversimplifies the complex and dynamic nature of macrophage activation, which involves a range of stimuli and signaling pathways. The authors argue that macrophages do not form stable subsets but respond to a combination of factors in their environment. They emphasize the need for a more comprehensive understanding of macrophage activation, considering the interplay of various signals and the context in which they occur. The article concludes that the M1/M2 paradigm, while useful, requires reassessment to better reflect the complexity of macrophage functions in health and disease.