Critical illness and the inflammatory response

The course of critical illness and the systemic inflammatory response is primarily determined by the patientʹs reaction to noxious stimuli such as infection and surgical trauma. The extent of an individualʹs phenotypic expression of inflammatory mediators is determined by genetic variability in the endogenous mediators constituting the pathways of inflammation and by environmental influences. Genes responsible for encoding the proteins involved in the transduction of inflammatory processes are therefore partially responsible for individual differences in systemic inflammatory responses to injury. The genetically determined capacity for cytokine production and release, heat shock protein expression, nitric oxide synthase activity, gene polymorphisms of coagulation factors or factors of innate immunity, such as defensins, and the genes involved in signal transduction may all contribute to a wide range of clinical manifestations of inflammation. The identification of certain genotypes that predispose to an accelerated inflammatory response, may allow for the development of generally-based therapy targeted at specific mediator that ultimately may reduce morbidity in critically ill patients.