ABSTRACT
The inflammatory response is a protective host defense mechanism mediated by the activation of soluble plasma factors and immune competent cells, including neutrophils, monocytes, macrophages, and endothelial cells. The inflammatory cascade is designed to upgrade the immunological response and assist with the eradication of microorganisms; however, an excessive response by inflammatory mediators leads to the deleterious effects that are part of the syndrome of sepsis. Tumor necrosis factor influences a number of leukocyte functions and is thought to be intimately involved in leukocyte activation during sepsis. In humans with the sepsis syndrome, preliminary evidence suggested that a dose-related increase in survival rate occurred after treatment with IL-1ra. The use of a combination of human IL-lra and a dimeric tumor necrosis factor binding protein in a Pseudomonas model of sepsis in neutropenic rats was uniformly fatal, although each agent alone conferred some benefit.
