Review: Immunotherapy

Comments

Immunomodulatory therapies aimed at reducing the systemic inflammatory response to sepsis have repeatedly been shown in clinical trials to have no effect on mortality in the critically ill. This excellent review examines the reasons for this failure especially when preclinical animal experiments showed benefits from these strategies.

The definitions for sepsis used for entry into clinical trials are questioned, especially when no microbiological distinctions are made between different types of sepsis. The measurement of inflammatory mediators (against which these therapies are aimed) are similarly ignored and examples given where immunomodulatory therapy has been given to large numbers of patients who never showed elevated levels of the inflammatory mediator.

The pathophysiology of the inflammatory response is considered and the validity of transposing results from septic animal models into the human clinical environment questioned. The role of corticosteroids, anti-endotoxin, interleukin-1 receptor antagonist, and anti-tumour necrosis factor therapies in sepsis are reviewed. Perhaps insufficient doses of these therapies are being used with the result that the mediator of interest is not blocked, or else this mediator may just not be clinically important in determining outcome.