Abstract
The cytokine storm is a marker of severity of various diseases and increased mortality. The altered metabolic profile and energy generation of immune cells affects their activation, exacerbating the cytokine storm. Currently, the emerging field of immunometabolism has highlighted the importance of specific metabolic pathways in immune regulation. The glycolytic enzyme pyruvate kinase M2 (PKM2) is a key regulator of immunometabolism and bridges metabolic and inflammatory dysfunction. This enzyme changes its conformation thus walks in different fields including metabolism and inflammation and associates with various transcription factors. This review summarizes the vital role of PKM2 in mediating immunometabolic reprogramming and its role in inducing cytokine storm, with a focus on providing references for further understanding of its pathological functions and for proposing new targets for the treatment of related diseases.
Highlights
The cytokine storm is defined as an overreaction of the immune system, which excessively activates macrophages and lymphocytes, and acutely secretes and releases high levels of proinflammatory cytokines resulting in a severe inflammatory response [1]
Thoracic aortic aneurysm and dissection increases secretion of pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS) [147]. These findings show that pyruvate kinase M2 (PKM2) plays a key role in inflammasome activation, and indicate that PKM2 can be pharmacologically targeted for treatment of inflammatory diseases and to alleviate cytokine storm
The cytokine storm is an overreaction of immune system, which excessively activates immune cells, resulting in secretion and release of high levels of proinflammatory cytokines leading to lethal inflammation
Summary
The cytokine storm is defined as an overreaction of the immune system, which excessively activates macrophages and lymphocytes, and acutely secretes and releases high levels of proinflammatory cytokines resulting in a severe inflammatory response [1]. Several novel studies have revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Studies report that PKM2 plays an important role in the development of some inflammatory diseases. Many studies demonstrated that PKM2-mediated immunometabolic reprogramming regulates the levels of cytokines through multiple pathways. PKM2 and Cytokine Storm promotes release of large amounts of proinflammatory cytokines, causing an excessive inflammatory response. This study reviews the pathways implicated in PKM2-mediated immunometabolic reprogramming and their contribution to the cytokine storm. The findings of the study will provide a basis for the development of novel therapies for managing the cytokine storm and other inflammatory diseases
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