Scriabin

REVIEW ARTICLE doi: 10.1111/j.1365-3083.2009.02255.x..................................................................................................................................................................

Innate Immune Responses to Danger Signals in Systemic Inflammatory Response Syndrome and Sepsis
A. Castellheim*, O.-L. Brekke , à, T. Espevik§, M. Harboe* & T. E. Mollnes*, , àAbstract
*Institute of Immunology, Rikshospitalet University Hospital and University of Oslo, Oslo, Norway;  Department of Laboratory Medicine, Nordland Hospital, Bodø, Norway; àInstitute of MedicalBiology, University of Tromsø, Tromsø, Norway; and §Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Received 6 February 2009;Accepted in revised form 11 March 2009 Correspondence to: A. Castellheim, Institute of Immunology, Rikshospitalet University Hospital, 0027 Oslo, Norway. E-mail: castellheim@ msn.com

The systemicimmune response induced by non-infectious agents is called systemic inflammatory response syndrome (SIRS) and infection-induced systemic immune response is called sepsis. The host inflammatory responsein SIRS and sepsis is similar and may lead to multiple organ dysfunction syndrome (MODS) and ultimately death. The mortality and morbidity in SIRS and sepsis (i.e. critical illness) remain highdespite advances in diagnostic and organ supporting possibilities in intensive care units. In critical illness, the acute immune response is organized and executed by innate immunity influenced by theneuroendocrine system. This response starts with sensing of danger by pattern-recognition receptors on the immune competent cells and endothelium. The sensed danger signals, through specific signallingpathways, activate nuclear transcription factor jB and other transcription factors and gene regulatory systems which up-regulate the expression of pro-inflammatory mediators. The plasma cascades are also...