What is a cytokine storm?
A cytokine storm is a dangerous overreaction of the immune system in which signalling molecules accumulate and can cause organ damage. How best to treat this remains largely an open question.
Cytokines are small proteins that immune cells use to communicate with one another. Under normal circumstances, they coordinate a response to an infection or injury. In a cytokine storm, this signalling system goes completely out of control: cytokine concentrations in the blood rise to extreme levels, after which the immune system can no longer put the brakes on itself.
What makes the situation dangerous is a self-reinforcing chain of events. Elevated cytokine concentrations drive immune cells into a particular form of cell death that releases even more cytokines. Neighbouring cells are affected, and they in turn do the same. That cycle can escalate until tissues and organs are damaged, sometimes with fatal consequences.
A cytokine storm can be triggered by a wide range of causes: infections (such as in sepsis or severe bacterial diseases), autoimmune diseases, hereditary conditions, and also medical treatments. Modern cancer therapies that powerfully activate T cells, such as CAR-T cell therapy, cause a variant called 'cytokine release syndrome' in up to one third of patients. In some cases, a more serious hyperinflammatory complication also occurs alongside this syndrome, including neurotoxicity.
Treatment has, until now, proved surprisingly difficult. Decades of research into blocking cytokines in sepsis have not yet produced a proven therapy. For treatment-related forms, such as the complications of CAR-T therapy, the optimal approach has also not yet been established. Research in this area is ongoing.
Based on multiple review articles and clinical studies (PMID 41540062, 33264547, 28555385, 34002066, 29907163, 31944278, 36906275, 40316520). The mechanism of the self-reinforcing feedback loop is based on a single source and is therefore less solid than the other findings.