THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) - IMMUNOLOGY AND POTENTIAL IMMUNOTHERAPY

Despite widespread advances in intensive care practices, and more potent and effective antimicrobials, septic shock continues to have a mortality rate of greater than 40%. Although antimicrobials can treat the etiologic organism, they do not alter the host response. It is becoming clear that invading organisms and other insults induce the release of cytokines and secondary mediators by the host. These mediators produce alterations in cellular, metabolic and physiologic functions producing the clinical picture of septic shock. Recent advances in cellular and molecular biology have permitted the identification of some of the mediators involved in this inflammatory cascade. Potential therapies are being developed which block or interrupt their activity. Treatment populations must be meticulously defined if we are to extract useful information concerning the efficacy of these new treatment modalities. In the following, proposed definitions for clinical patterns seen in patients with sepsis, and their inherent problems when applied to pediatrics are discussed. The pathophysiology of sepsis is discussed, and specific therapies designed to interrupt the inflammatory cascade are examined.