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Molecular biology of inflammation and sepsis: A primer*

Cinel, Ismail MD, PhD; Opal, Steven M. MD

doi: 10.1097/CCM.0b013e31819267fb
Concise Definitive Review

Background: Remarkable progress has been made during the last decade in defining the molecular mechanisms that underlie septic shock. This rapidly expanding field is leading to new therapeutic opportunities in the management of severe sepsis.

Aim: To provide the clinician with a timely summary of the molecular biology of sepsis and to better understand recent advances in sepsis research.

Data Selection: Medline search of relevant publications in basic mechanisms of sepsis/severe sepsis/septic shock, and selected literature review of other manuscripts about the signalosome, inflammasome, apoptosis, or mechanisms of shock.

Data Synthesis and Findings: The identification of the toll-like receptors and the associated concept of innate immunity based upon pathogen- or damage-associated molecular pattern molecules allowed significant advances in our understanding of the pathophysiology of sepsis. The essential elements of the inflammasome and signal transduction networks responsible for activation of the host response have now been characterized. Apoptosis, mitochondrial dysfunction, sepsis-related immunosuppression, late mediators of systemic inflammation, control mechanisms for coagulation, and reprogramming of immune response genes all have critical roles in the development of sepsis.

Conclusions: Many of these basic discoveries have direct implications for the clinical management of sepsis. The translation of these “bench-to-bedside” findings into new therapeutic strategies is already underway. This brief review provides the clinician with a primer into the basic mechanisms responsible for the molecular biology of sepsis, severe sepsis, and septic shock.

From the Division of Critical Care Medicine (IC), The Robert Wood Johnson School of Medicine, The University of Medicine and Dentistry of New Jersey, Camden NJ; and The Infectious Disease Division (SMO), Memorial Hospital of RI, The Warren Alpert School of Medicine of Brown University, Providence, RI.

Dr. Opal has received grants from Wyeth and Eisai Inc. Dr. Cinel has not disclosed any potential conflicts of interest.

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© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins