Systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome in sepsis.

the concepts of SIRS and CARS still exist, although the notion that CARS represents a reaction to SIRS has been challenged [3, 4] . In this theme issue of the Journal of Innate Immunity, current knowledge of several aspects of the SIRS and CARS concepts are reviewed in 7 articles; the issue is completed by 3 original articles about these topics. Kumpf and Schumann [5] summarize data on genetic variations in Toll-like receptors and cytokines (important components of the host response to sepsis) and their impact on the course of severe infection. These authors also analyzed evidence coming from animal experiments showing that adequate triggering of Toll-like receptors and cytokine production are needed for containment of infections. McCall and colleagues [6] discuss the role of epigenetic processes of innate immune cells (i.e. changes in the phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence) during infection accompanied by SIRS, describing the host response in 4 stages: homeostasis, incitement, evolution and resolution. Coll and O’Neill [7] contribute with an extensive overview of the role of Tolllike receptors and Nod-like receptors in the induction of an innate immune response to pathogens. In addition, they discuss negative regulators of these pathways, which on the one hand seek to dampen excessive inflammation In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a consensus meeting to define the systemic inflammation that was recognized to accompany severe infection and sterile trauma. A year later, the ACCP/SCCM Consensus Conference introduced the term ‘systemic inflammatory response syndrome’ or SIRS in its meeting report [1] . SIRS was (and still is) considered to be present when patients have 2 or more of the following clinical findings: body temperature 1 38 ° C or ! 36 ° C; heart rate 1 90/min; hyperventilation evidenced by a respiratory rate of 1 20/min or a PaCO 2 of ! 32 mm Hg, and a white blood cell count of 1 12,000 cells/ l or ! 4,000 cells/ l. It was appreciated that SIRS could be the consequence of different underlying conditions, including infection, trauma and other types of sterile injury. Since then, sepsis is defined as documented or suspected infection with evidence of systemic inflammation, consisting of 2 or more SIRS criteria. In 1996, Roger Bone (1941–1997), who had been the chair of the ACCP/SCCM Consensus Conference, introduced a second acronym to portray the host response during sepsis, CARS or ‘compensatory anti-inflammatory response syndrome’, seeking to describe an immunological phenomenon that was increasingly noticed to occur in sepsis, characterized by the induction of several anti-inflammatory mechanisms [2] . Nowadays, Published online: July 5, 2010 Journal of Innate Immunity