The Systemic Pro-Inflammatory Response in Sepsisde Jong H.K.a · van der Poll T.a, b · Wiersinga W.J.a, b
aCenter for Molecular Medicine and bDepartment of Internal Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Dr. Willem Joost Wiersinga
Department of Internal Medicine
Academic Medical Centre, University of Amsterdam
Room G2-132, Meibergdreef 9, NL–1105 AZ Amsterdam (The Netherlands)
Tel. +31 20 566 9111, Fax +31 20 697 7192, E-Mail firstname.lastname@example.org
Keywords: Systemic inflammatory response syndromeSepsisCytokinesToll-like receptorsCoagulationMigration inhibitory factorMyeloid-related protein 8Myeloid-related protein 14High-mobility group box-1Triggering receptor expressed on myeloid cells-1ComplementC5aMultiorgan failure
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The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase proteins while the predominant cellular components are leukocytes and the endothelium. High-throughput genetic profiling studies have led to increased insights into leukocyte regulation during sepsis. New players in the pro-inflammatory cytokine network include interleukin-17, high-mobility group box-1 protein, macrophage migration inhibitory factor, the myeloid-related proteins Mrp8 and Mrp14, and soluble triggering receptor expressed on myeloid cells-1. Activation of coagulation with concurrent downregulation of anticoagulant systems and fibrinolysis are almost universally present in septic patients with SIRS. Increasing evidence points to an extensive cross-talk between inflammation and coagulation, in which the protease-activated cell receptors play an important role. Sepsis causes excessive activation of the complement system in which C5a plays a key part. Further dissection of the role of host-pathogen interactions, the cytokine network, the coagulation cascade, the complement system and their multidirectional interactions in sepsis will pave the way for new treatment targets that can modify the excessive and collective activation of all these systems.
© 2010 S. Karger AG, Basel
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