Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome

Figure 1

Development of cytokine release syndrome. (a) Antigen presentation: when DAMPs (damage-associated molecular patterns) or PAMPs (pathogen-associated molecular patterns) bind to PRRs (pattern recognition receptors) on the membrane of antigen-presenting cells (APCs) in capillaries, these cells activate immune signal transduction and stimulate immune cells and epithelial cells to release cytokines. (b) Activation of the innate immune system: cytokine secretion results in the recruitment of innate immune cells (e.g., macrophages, neutrophils, and NK cells) in local tissues. (c) Activation of adaptive immune system: innate immune cells further activate adaptive immune cells (T cells and B cells). Immune cells then continue to activate each another, resulting in extensive production of cytokines under the action of positive feedback and causing the formation of a cytokine storm. (d) Cytokine release syndrome: after a cytokine storm is formed, immune cells and the cytokines released by them continue to induce capillary leakage and pyroptosis, which can lead to severe organ structural destruction and functional failure. IP-10: interferon-inducible protein 10; MIP: macrophage inflammatory protein; GM-CSF: granulocyte-macrophage colony-stimulating factor; IL: interleukin; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-γ; NK cells: natural killer cells.