A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Normally, cytokines are part of the body's immune response to infection, but their sudden release in large quantities can cause multisystem organ failure and death.
Cytokine storms can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H1N1 influenza, H5N1 influenza, SARS-CoV-1, and SARS-CoV-2, Influenza B, Parainfluenza virus. Other causative agents include the Epstein-Barr virus, cytomegalovirus, group A streptococcus, and non-infectious conditions such as graft-versus-host disease. The viruses can invade lung epithelial cells and alveolar macrophages to produce viral nucleic acid, which stimulates the infected cells to release cytokines and chemokines, activating macrophages, dendritic cells, and others.
Cytokine storm syndrome is a diverse set of conditions that can result in a cytokine storm. Cytokine storm syndromes include familial hemophagocytic lymphohistiocytosis, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis.
The term "cytokine storm" is often loosely used interchangeably with cytokine release syndrome (CRS) but is more precisely a differentiable syndrome that may represent a severe episode of cytokine release syndrome or a component of another disease entity, such as macrophage activation syndrome. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset (fulminant) CRS appears to be a cytokine storm.
Nicotinamide (a form of vitamin B3) is a potent inhibitor of proinflammatory cytokines.