Infliximab reverses growth hormone resistance associated with inflammatory bowel disease

Aliment Pharmacol Ther. 2005 May 1;21(9):1063-71. doi: 10.1111/j.1365-2036.2005.02449.x.

Abstract

Background: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance.

Aim: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis.

Methods: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit.

Results: Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 showed significant negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = -0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment.

Conclusions: Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin-like growth factor-1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Drug Resistance
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Human Growth Hormone / blood*
  • Humans
  • Infliximab
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged

Substances

  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Infliximab