[Pathophysiological basis of surgery-linked sepsis].
Infection or injury, including surgical procedures, induces an inflammatory response of the host organism. This immune response must be finely tuned and precisely regulated, because deficiencies or excesses of the inflammatory response cause morbidity and shorten the lifespan. Activated receptors of the innate immune system (pattern recognition receptors, PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) including injured tissue-associated intracellular proteins (alarmins), lead to an exaggerated immune response. This is characterized by a complex interplay of cytokines, chemokines, complement and coagulation factors as well as inflammatory and immune regulatory cells. There is increasing recognition that the major pathophysiologic event in sepsis is the progression from the initial hyperinflammatory state to an immunosuppressive state in which the host is unable to eradicate invading pathogens and particularly prone to develop secondary nosocomial infections and organ damage. Surgical trauma-associated immune dysfunction per se predisposes the host to surgery-related sepsis. Immune suppression is mediated by massive apoptosis-induced depletion of lymphocytes and dendritic cells, decreased expression of the cell surface antigen complex HLA-DR and increased expression of negative costimulatory molecules. Besides increased numbers of regulatory T cells there is a shift from a phenotype of inflammatory Th1 cells to an antiinflammatory phenotype of Th2 cells characterized by the production of interleukin-10. Key mediators of sepsis are HMGB1, MIF and complement factor C5a. With the identification of central pathomechanistic events, e.g. amplification of the coagulation, complement and inflammation cascades, immune dysbalance and neuroimmunomodulation via the cholinergic anti-inflammatory reflex, the opportunity now exists to apply these insights to the development of new and novel therapeutics aimed at modulating rather than inhibiting the systemic host response to infection.
Institut für Experimentelle Chirurgie, Medizinische Fakultät, Universität Rostock, Schillingallee 69a, Rostock, Germany. brigitte.vollmar@med.uni-rostock.de
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B
Vollmar
D001424:Bacterial Infections / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D003428:Cross Infection / Q000276:immunology* / Q000401:mortality; D004211:Disseminated Intravascular Coagulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D018655:Lymphocyte Count; D009102:Multiple Organ Failure / Q000276:immunology; D015213:Neuroimmunomodulation / Q000502:physiology; D051192:Receptors, Pattern Recognition / Q000502:physiology; D018805:Sepsis / Q000276:immunology* / Q000401:mortality; D015398:Signal Transduction / Q000502:physiology; D013530:Surgical Wound Infection / Q000276:immunology* / Q000401:mortality; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors
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