Agents to reduce cytokine storm.

The increasing insight into pathomechanisms of dysregulated host response in several inflammatory diseases led to the implementation of the term "cytokine storm" in the literature more than 20 years ago. Direct toxic effects as well as indirect immunomodulatory mechanisms during cytokine storm have been described and were the basis for the rationale to use several substances and devices in life-threatening infections and hyperinflammatory states. Clinical trials have been performed, most of them in the form of minor, investigator-initiated protocols; major clinical trials focused mostly on sepsis and septic shock. The following review tries to summarize the background, pathophysiology, and results of clinical investigations that had implications for the development of therapeutic strategies and international guidelines for the management of hyperinflammation during syndromes of cytokine storm in adult patients, predominantly in septic shock.