Molecular and Cellular Mediators of the Inflammatory Response

Abstract

Inflammation is a highly complex process involving vascular, neurogenic, humoral, and cellular responses. Although the descriptive features of acute inflammation have long been known (i.e., heat, redness, pain, swelling), a single satisfactory definition of this phenomenon is still lacking. Successful therapy for inflammation rests not only on investigating the type of injury, but also on the timing of the intervention. This review focuses on humoral and cellular responses to injury, defining essential and interrelated inflammatory pathways. Systemic inflammatory response system (SIRS), in relation to sepsis syndrome, is defined by the global proinflammatory physiologic response to a stimulus. In contrast, compensatory antiinflammatory response (CARS) results from a predominant antiinflammatory response to an insult, also causing immunosuppression and increased susceptibility to infection. Also discussed are the roles of cytokines, adhesion molecules, inflammatory cells such as neutrophils, mast cells, and lymphocytes, extracellular vesicles, sphingolipids, reactive oxygen metabolites, nitric oxide, the complement cascade, and eicosanoids. Therapeutic implications and trials are examined in relation to cytokines in SIRS and CARS, activated protein C, and inflammatory bowel disease. This review contains 11 figures, 4 tables, and 79 references.