Impact of infliximab on serum leptin levels in patients with Crohn's disease

J Clin Endocrinol Metab. 2005 Jun;90(6):3510-6. doi: 10.1210/jc.2004-1222. Epub 2005 Mar 22.


Objectives: In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of inflammation-induced cachexia in Crohn's disease (CD). The regulation of leptin by TNFalpha is poorly understood in CD. Pharmacological neutralization of TNFalpha with infliximab offers a unique opportunity to study TNFalpha-mediated regulation of leptin in CD patients.

Methods: We prospectively followed up CD patients treated with infliximab (n = 20). Body composition was assessed before and after treatment at 1 and 4 wk. Serum leptin, IL-6, soluble TNF receptor type II, and soluble intercellular antiadhesion molecule-1 levels were measured as well as cholesterol levels and free urinary cortisol. Because methylprednisolone (MP) increases leptin production in vivo, CD patients treated with MP (n = 9) were studied separately as a positive control group.

Results: Infliximab induced clinical remission and a significant decrease in C-reactive protein (P < 0.01) and IL-6 (P < 0.05) levels in all CD patients and increased body weight (P = 0.013) at 4 wk. Leptinemia was significantly increased after infliximab administration at 1 wk (P = 0.014) and 4 wk (P < 0.001). This increase in serum leptin occurred early at 1 wk, when no significant weight and fat mass changes could be observed and was associated with the down-regulation of TNFalpha-regulated mediators, soluble TNF receptor type II (P = 0.015), and soluble intercellular antiadhesion molecule-1 (P = 0.007). Moreover, infliximab increased cholesterol levels at 1 wk (P = 0.001). Twenty-four-hour cortisol secretion was not altered by infliximab. Leptinemia increased at 1 wk after MP administration (P = 0.028).

Conclusion: Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers / blood
  • Body Mass Index
  • Crohn Disease / blood*
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Infliximab
  • Interleukin-6 / blood
  • Leptin / blood*
  • Male
  • Receptors, Leptin
  • Receptors, Tumor Necrosis Factor, Type II / blood
  • Regression Analysis
  • Tumor Necrosis Factor-alpha / physiology
  • Weight Gain / drug effects


  • Antibodies, Monoclonal
  • Biomarkers
  • Interleukin-6
  • LEPR protein, human
  • Leptin
  • Receptors, Leptin
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Infliximab