Cytokine Storm - Cause

Cause

When the immune system is fighting pathogens, cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines. Normally, this feedback loop is kept in check by the body. However, in some instances, the reaction becomes uncontrolled, and too many immune cells are activated in a single place. The precise reason for this is not entirely understood but may be caused by an exaggerated response when the immune system encounters a new and highly pathogenic invader. Cytokine storms have potential to do significant damage to body tissues and organs. If a cytokine storm occurs in the lungs, for example, fluids and immune cells such as macrophages may accumulate and eventually block off the airways, potentially resulting in death.

The cytokine storm (hypercytokinemia) is the systemic expression of a healthy and vigorous immune system resulting in the release of more than 150 known inflammatory mediators (cytokines, oxygen free radicals, and coagulation factors). Both pro-inflammatory cytokines (such as Tumor necrosis factor-alpha, Interleukin-1, and Interleukin-6) and anti-inflammatory cytokines (such as interleukin 10 and interleukin 1 receptor antagonist) are elevated in the serum of patients experiencing a cytokine storm.

Cytokine storms can occur in a number of infectious and non-infectious diseases including graft versus host disease (GVHD), acute respiratory distress syndrome (ARDS), sepsis, avian influenza, smallpox, and systemic inflammatory response syndrome (SIRS). Cytokine storm may also be induced by certain medications. The experimental drug TGN1412 caused extremely serious symptoms likely due to a cytokine storm when given to six participants in a Phase I trial.

The first reference to the term cytokine storm in the published medical literature appears to be by Ferrara et al. in GVHD in February 1993.