title: Skeletal muscle contractile properties and proinflammatory cytokine gene expression in human endotoxaemia.
abstract: BACKGROUND
  Muscle dysfunction associated with sepsis contributes to morbidity and mortality but the underlying mechanisms are unclear. This study examined whether muscle weakness relates to an intrinsic defect in contraction, or to central mechanisms associated with acute illness, and whether systemic endotoxaemia induces changes in gene expression for proinflammatory cytokines within human muscle in vivo.
  
  
  METHODS
  In this experimental study, 12 healthy men received intravenous Escherichia coli lipopolysaccharide (LPS, 4 ng/kg) or saline (control). Voluntary and electrically stimulated quadriceps contraction, and tumour necrosis factor (TNF) alpha mRNA expression in quadriceps muscle biopsies were studied before and after the infusion.
  
  
  RESULTS
  Endotoxaemia induced transient weakness of voluntary quadriceps contraction, equivalent to a 7.8 (95 per cent confidence interval 2.1 to 13.5) per cent reduction in contractile force at 180 min (P = 0.027) and a 9.0 (5.2 to 12.8) per cent reduction at 300 min (P = 0.008). Electrically stimulated contraction was unaffected. LPS administration resulted in an apparent fibre-specific induction of TNF-alpha mRNA.
  
  
  CONCLUSIONS
  Endotoxaemia results in a reduction in voluntary muscle contractile force without an apparent defect in stimulated muscle contraction. Loss of volition may be a more important factor than intrinsic dysfunction in acute sepsis-associated human muscle weakness.
authors.affiliation: Infection, Injury and Inflammation Research Group, Salford Royal NHS Foundation Trust, Hope Hospital, Salford, UK.
authors.forename: F J
authors.initials: FJ
authors.lastname: McNicol
authors.forename: J A
authors.initials: JA
authors.lastname: Hoyland
authors.forename: R G
authors.initials: RG
authors.lastname: Cooper
authors.forename: G L
authors.initials: GL
authors.lastname: Carlson
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D004558:Electric Stimulation; D019446:Endotoxemia / Q000503:physiopathology*; D004926:Escherichia coli; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018908:Muscle Weakness / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha