title: Infliximab reverses inflammatory muscle wasting (sarcopenia) in Crohn's disease.
abstract: BACKGROUND
  Muscle wasting or sarcopenia arising from chronic inflammation is found in 60% of patients with Crohn's disease. Transcriptional protein NF-κB reduces muscle formation through MyoD transcription and increases muscle breakdown by proteolysis.
  
  
  OBJECTIVE
  As TNF is a potent activator of NF-κB, and anti-TNF agent infliximab (IFX) prevents NF-κB activation, to determine whether or not Crohn's patients treated with IFX gain muscle volume and strength.
  
  
  METHODS
  We performed a prospective, repeated-measures cohort study in adult Crohn's disease patients with an acute disease flare. Patients were instructed not to vary diet or activity. Concomitant medications were kept stable. At week 1 (pre-treatment), week 16 (post-IFX induction) and week 25 (post-first IFX maintenance dose), we assessed (i) MRI volume of quadriceps femoris at anatomical mid-thigh; (ii) maximal concentric quadriceps contractions strength at three specific speeds of contraction; (iii) physical activity by validated instrument (IPAQ); (iv) Three-day food record of intake and composition (food-weighing method); (v) Serum levels of IL6.
  
  
  RESULTS
  Nineteen patients (58% female; mean age 33.2 ± 10.7 years) were recruited. IFX increased muscle volume in both legs from baseline (right, 1505 cm(3) ) to week 25 (right, 1569 cm(3) ; P = 0.010). IFX also increased muscle strength in both legs from baseline (right 30°/s, 184.8 Nm) to week 25 (right 30°/s, 213.6 Nm; P = 0.002). Muscle volume gain correlated with male gender (P = 0.003). Significant gains in muscle volume and strength were unrelated to prednisolone use. Serum IL6 levels decreased by week 25 (P = 0.037).
  
  
  CONCLUSIONS
  The anti-TNF agent infliximab reverses inflammatory sarcopenia in patients with Crohn's disease.
authors.affiliation: Gastroenterology and Hepatology Unit, Canberra Hospital, Garran, ACT, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Subramaniam
authors.forename: K
authors.initials: K
authors.lastname: Fallon
authors.forename: T
authors.initials: T
authors.lastname: Ruut
authors.forename: D
authors.initials: D
authors.lastname: Lane
authors.forename: R
authors.initials: R
authors.lastname: McKay
authors.forename: B
authors.initials: B
authors.lastname: Shadbolt
authors.forename: S
authors.initials: S
authors.lastname: Ang
authors.forename: M
authors.initials: M
authors.lastname: Cook
authors.forename: J
authors.initials: J
authors.lastname: Platten
authors.forename: P
authors.initials: P
authors.lastname: Pavli
authors.forename: D
authors.initials: D
authors.lastname: Taupin
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015331:Cohort Studies; D003424:Crohn Disease / Q000150:complications* / Q000188:drug therapy*; D004032:Diet; D015444:Exercise; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D016328:NF-kappa B / Q000096:biosynthesis; D011446:Prospective Studies; D055948:Sarcopenia / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab