Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome

Figure 3

The mechanism of organ damage in cytokine release syndrome. (a) The mechanism of brain damage in cytokine release syndrome. IL-6 and TNF-α act on the vascular endothelium to increase the permeability of the BBB and activate the astrocytes and microglia to release cytokines, impacting the structure and function of neurons and synapses. (b) The mechanism of lung injury in cytokine release syndrome. Immune cells are recruited to the lungs by IL-6 and activated by cytokines such as TNF and IFN, generating huge amounts of free radicals and proteases, causing pulmonary edema and gas exchange problems. (c) The mechanism of heart damage in cytokine release syndrome. TNF-α and IL-6 can increase oxidative stress, reduce eNOS phosphorylation, and cause coronary endothelial dysfunction. Excessive TNF-α binding to receptors on cardiomyocytes can cause myocardial damage and dysfunction. TNF-α, IL-6, and IL-1 regulate the expression and function of ion channels on myocardial cell membranes, leading to arrhythmia. (d) The mechanism of liver injury in cytokine release syndrome. IL-6 binds IL-6R across the membrane to exert an anti-inflammatory effect. When IL-6 levels rise, it can combine with sIL-6R to promote inflammation and induce the production of acute phase proteins, culminating in microthrombosis and liver amyloidosis. (e) The mechanism of kidney injury in cytokine release syndrome. IL-17 and TNF-α work synergistically to suppress NO production in the vascular endothelium and enhance blood vessel contraction. Due to the chemotaxis of cytokines, T cells are deposited in blood vessels and enter tissues to produce ROS, leading to kidney damage and renal fibrosis. Microthrombi entering the renal capillary network can easily form microinfarction foci, leading to acute necrosis of renal tubules. Abbreviations: BBB: blood–brain barrier; eNOS: endothelial nitric oxide synthase; sIL-6R: soluble IL-6 receptors; NO: nitric oxide.