title: [Pathophysiology of sepsis--will the basic research contribute to the improvement of outcome in clinical sepsis?].
abstract: In this decade, the molecular mechanism of sepsis has been strikingly clarified. Especially, the identification of toll-like receptors as the pivotal molecules for the recognition of the stimulation of the inflammatory products of microorganisms has contributed to the elucidation of intracellular signaling pathways which result in severe systemic inflammatory response in sepsis. The production and release of a variety of pro-inflammatory mediators have been found to be associated with severe systemic inflammation and multiple organ dysfunction syndrome (MODS). In the pathophysiology of the development of MODS in sepsis, the disturbance of peripheral microcirculation, the insult of tissues and cells by leukocytes and activated complements and the augmentation of the disorder of fibrinolytic and coagulation systems, which often results in the outbreak of disseminated intravascular coagulopathy (DIC), will be critically involved. Despite of the advance in the basic research regarding molecular pathophysiology of sepsis, sepsis is still accompanied by high mortality in clinical settings. Almost all clinical trials targeting sepsis-associated mediators have failed, except the substitution therapy of activated protein C. However, further trials based on the basic findings, including the therapies targeting the multiple mediators, will contribute to the improvement of outcome of clinical sepsis. ple organ dysfunction syndrome (MODS), pro-inflammatory mediator, disseminated intravascular coagulopathy (DIC).
authors.affiliation: Environmental Science Center, University of Tokyo, Tokyo 113-0033.
authors.forename: Risuke
authors.initials: R
authors.lastname: Karima
mesh_terms: D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D009102:Multiple Organ Failure / Q000209:etiology; D018805:Sepsis / Q000209:etiology* / Q000628:therapy*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D051193:Toll-Like Receptors