Inflammatory responses and mediators.
The host response to injury is usually appropriate in degree and is self-limited. In more severe injury, the host response may persist inappropriately, leading to SIRS and MODS and possibly multiple organ failure. The initial response to injury is mediated primarily by norepinephrine, and is directed toward preservation of circulation to the heart and brain at the expense of other vascular beds. If fluid resuscitation is adequate and necrotic tissue is débrided, a hypermetabolic state ensues, mediated by epinephrine and directed toward supporting repair of injured tissue by leukocytes. Inflammatory cells are recruited to the site of injury and elaborate cytokines, which promote repair locally, but in severe injury may be systemically released and trigger remote inflammation. Cytokine biology presently is poorly understood, and simple anticytokine strategies have failed to improve survival of critically ill patients. Current therapy of SIRS and MODS is directed toward symptoms. Presently, it is unclear how an abnormal stress response arises. Cytokine spillover into the systemic circulation may occur. Selective transcriptional failure may be the cellular basis of organ dysfunction. Inappropriate production of peroxynitrite or its precursor, NO, is implicated in mediating cellular injury in SIRS and MODS.
Kim
P K
PK
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Deutschman
C S
CS
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D016638:Critical Illness; D016207:Cytokines / Q000502:physiology; D003646:Debridement; D004837:Epinephrine / Q000502:physiology; D005440:Fluid Therapy; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D009102:Multiple Organ Failure / Q000209:etiology; D009638:Norepinephrine / Q000502:physiology; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D014947:Wounds and Injuries / Q000378:metabolism / Q000503:physiopathology*
D000316:Adrenergic alpha-Agonists; D016207:Cytokines; D018836:Inflammation Mediators; D009638:Norepinephrine; D004837:Epinephrine