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 """"""""overaction"""""""" and organ injury are not completely understood. In this study, we measure concentrations of Neutrophil Activating Protein (NAP), a recently described macrophage derived cytokine (now designated interleukin 8), in the serum of patients with septic shock and in the bronchoalveolar lavage fluid of patients with the adult Respiratory Distress Syndrome. NAP will be determined using a newly developed ELISA assay. Parallel studies are being conducted in the canine septic shock model examining both circulating levels of NAP and NAP concentrations in bronchoalveolar lavage. As part of this study we are also partially characterizing dog NAP by purifying it from stimulated canine alveolar macrophages. A new initiative in this project involves the identification and characterization of circulating IL-8 binding protein(s) in septic shock. This line of investigation arose from the finding of interference in the ELISA assay in some septic patients. This investigation will provide insight into the mechanisms or organ damage in septic shock. This understanding may lead to the development of new therapies for septic shock aimed at inhibiting or regulating potentially harmful endogenous mediators of the inflammatory response.
