Figure 1.

Kinetics of Cytokine Storms

Cytokine storms have many different underlying causes that can manifest with different kinetics.

(A) The solid line depicts the natural arc of an immune response to infection over a period of days to weeks that transitions to a resolution phase as a pathogen is controlled. For microorganisms with a high replicative potential, changes in the magnitude and duration of the immune response can result in systemic immune pathology. The two dotted lines illustrate different arcs associated with a cytokine storm through either an increased amplitude or a failure to enter the resolution phase.

(B) The rapid and widespread engagement of adaptive responses by bacterially derived superantigens or therapeutic interventions can lead to a rapid surge in immune activity (hour-days) associated with supra-physiological levels of circulating cytokines.

(C) Certain cancers that have a systemic component can lead to sustained (weeks to months) responses associated with elevated cytokine production. Likewise, chronic autoimmune diseases such as juvenile idiopathic arthritis (JIA) and lupus can have flares associated with increased cytokine production. There are also genetic defects closely linked to aberrant cytokine production, enhanced signaling, or a failure to fully control certain viral infections, which can cause periodic spikes in immune hyperactivity.