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Studies of the cytokine cascade in animal models of infection and human experiments involving endotoxin infusion have contributed fundamentally to understanding the role of cytokines in human sepsis. The complexity of this cytokine cascade has been difficult to unravel in clinical sepsis. However, the Jarisch-Herxheimer reaction has been identified as a model of the cytokine cascade in human sepsis and has provided an excellent model for experiments involving blocking agents. TNF blocking has been shown to be important for protection in animal models of sepsis, but has been somewhat disappointing in humans because adverse events have generally outweighed benefits.

Cytokines involved in human septic shock--the model of the Jarisch- Herxheimer reaction