Neutrophil activation with subsequent damage to host tissues during septicemia has been implicated in the cascade of events that lead to multiple organ failure (MOF). MOF is associated with over half of all deaths from septic shock. The mediators and mechanisms responsible for neutrophil """"""""overactivation"""""""" and organ injury are not completely understood. In this study, we have measured concentrations of Neutrophil Activating Protein-I (NAP-I), a recently described macrophage derived cytokine (now designated Interleukin 8), in the serum of patients with septic shock. IL- 8 concentrations were found to correlate with the severity of illness and IL-6 and TNF concentrations. A recent initiative in this project involved the identification and characterization of circulating IL-8 binding protein(s) in plasma. This line of investigation arose from the finding of interference in the ELISA assay in some septic patients (J Immunol, 1993). Further, in vitro priming by IL-8 has been examined in detail (manuscript in preparation, 1995) and mechanisms that control IL-8 production have been investigated (manuscript in preparation, 1995). This investigation has provided insight into the role and actions of IL-8 in septic shock. This understanding may help in the development of new therapies for septic shock aimed at inhibiting or regulating potentially harmful endogenous mediators of the inflammatory response. This research project, except for submitting results for publication, has been completed.
