Molecular biology of inflammation and sepsis: a primer.
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.


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


METHODS
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.
Cinel
Ismail
I
Division of Critical Care Medicine, The Robert Wood Johnson School of Medicine, The University of Medicine and Dentistry of New Jersey, Camden, NJ, USA. cinel-ismail@cooperhealth.edu
Opal
Steven M
SM
D000818:Animals; D001777:Blood Coagulation; D016207:Cytokines; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D008967:Molecular Biology; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D018805:Sepsis / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000502:physiology
D016207:Cytokines; D051193:Toll-Like Receptors