SEPSIS SYNDROMES AND TOXIC SHOCK SYNDROMES - CONCEPTS IN PATHOGENESISAND A PERSPECTIVE OF FUTURE TREATMENT STRATEGIES

Production of cytokines by host cells in response to infectious stimul i is a dynamic process resulting in a full range of biologic effects, from enhancement of cell function to septic shock and organ failure. I nteractions of the various cytokines afford a second level of cellular control. It is now clear that these interactions can be inhibitory, a dditive, or even synergistic. The clinical importance of these interac tions is suggested by studies demonstrating that monoclonal antibodies against several cytokines may each be protective in endotoxin shock m odels. Just as the past 5 years have seen great progress in the unders tanding of individual cytokines, the next 5 years will largely be spen t investigating the complex interrelationships of all known cytokines and growth factors, with an eye toward potential therapeutic intervent ions. Though patients with infections of a variety of types may all de velop shock, the clinical presentations may be quite different. This r eview describes the progressive stages of severe infection, some clini cal differences between gram-positive and gram-negative infections and the toxic shock syndromes, and attempts to correlate these difference s with differences in the cytokine cascade elicited by various infecti ous agents.