INHIBITORS OF COMPLEMENT AND NEUTROPHILS - A CRITICAL-EVALUATION OF THEIR ROLE IN THE TREATMENT OF SEPSIS

Objective: Damage to the vascular system is a major finding of sepsis and its sequelae. This damage is caused, in part, by the recruitment and adhesion of neutrophils to the endothelium and their release of destructive molecules. Mediators released by various cell types, including the neutrophil itself, control these destructive actions of the neutrophil. The complement system is one such group of mediators. Through the use of medications that decrease neutrophil activation and adherence and block complement activation, it may be possible to control the course of sepsis. Data Sources: The issues discussed in this paper come from a wide variety of sources, including several broad-based clinical studies of humans with inflammatory disease. Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics. Study Selection: This article reviews a subject that is rapidly evolving, with frequent new discoveries. Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals. Few clinical studies have been performed using these agents. Data Extraction: Most cited literature was found in reputable, peer review journals, including important basic science and clinical journals such as Science, Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine. Data Synthesis: Occasionally, contradictions do occur in the results of various studies. These contradictions are discussed and may often be due to different protocols and different definitions of the various clinical states. Conclusions: Pentoxifylline has been shown to decrease neutrophil adhesion and provides increased survival rate in various animal models of sepsis. Early studies regarding monoclonal antibodies to adhesion molecules are exciting. However, the possible effects of these agents in sepsis has yet to be studied. Drugs have been discovered that show potential to block the numerous destructive agents released by degranulating neutrophils.