Statins and sepsis: multiple modifications at multiple levels

TY - JOUR

T1 - Statins and sepsis

T2 - multiple modifications at multiple levels

AU - Terblanche, Marius

AU - Almog, Yaniv

AU - Rosenson, Robert

AU - Smith, Terry S.

AU - Hackam, Daniel G.

PY - 2007/5

Y1 - 2007/5

N2 - Sepsis, an infection-induced inflammatory syndrome, is a leading and increasing cause of mortality worldwide. Animal and human observational studies suggest statins may prevent the morbidity and mortality associated with the sepsis syndrome. In this Review, we describe the demonstrated mechanisms through which statins modulate the inflammatory response associated with sepsis. These mechanisms include effects on cell signalling with consequent changes at the transcriptional level, the induction of haem oxygenase, the direct alteration of leucocyte-endothelial cell interaction, and the reduced expression of MHC II. Since statins do not target individual inflammatory mediators, but possibly reduce the overall magnitude of the systemic response, this effect could prove an important distinguishing feature modulating the host response to septic insults. This work establishes the biological plausibility needed for future trials of statins in critical illness.

AB - Sepsis, an infection-induced inflammatory syndrome, is a leading and increasing cause of mortality worldwide. Animal and human observational studies suggest statins may prevent the morbidity and mortality associated with the sepsis syndrome. In this Review, we describe the demonstrated mechanisms through which statins modulate the inflammatory response associated with sepsis. These mechanisms include effects on cell signalling with consequent changes at the transcriptional level, the induction of haem oxygenase, the direct alteration of leucocyte-endothelial cell interaction, and the reduced expression of MHC II. Since statins do not target individual inflammatory mediators, but possibly reduce the overall magnitude of the systemic response, this effect could prove an important distinguishing feature modulating the host response to septic insults. This work establishes the biological plausibility needed for future trials of statins in critical illness.

KW - C-REACTIVE PROTEIN

KW - COA REDUCTASE INHIBITORS

KW - HUMAN ENDOTHELIAL-CELLS

KW - NITRIC-OXIDE SYNTHASE

KW - VASCULAR SMOOTH-MUSCLE

KW - INTENSIVE-CARE UNITS

KW - POPULATION-BASED COHORT

KW - NECROSIS-FACTOR-ALPHA

KW - PPAR-GAMMA LIGANDS

KW - NF-KAPPA-B

U2 - 10.1016/S1473-3099(07)70111-1

DO - 10.1016/S1473-3099(07)70111-1

M3 - Literature review

SN - 1473-3099

VL - 7

SP - 358

EP - 368

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

IS - 5

ER -