title: Impact of infliximab on serum leptin levels in patients with Crohn's disease.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.
authors.affiliation: Division of Gastroenterology, Montreal General Hospital, McGill University, 1650 Cedar Avenue, D7.102, Montreal, Quebec, Canada H3A 1A4. denis.franchimont@mcgill.ca
authors.forename: Denis
authors.initials: D
authors.lastname: Franchimont
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roland
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.forename: Eric
authors.initials: E
authors.lastname: Quertinmont
authors.forename: Youssef
authors.initials: Y
authors.lastname: Toubouti
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Gervy
authors.forename: Jacques
authors.initials: J
authors.lastname: Deviere
authors.forename: Andre
authors.initials: A
authors.lastname: Van Gossum
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood*; D008297:Male; D054411:Receptors, Leptin; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D015850:Interleukin-6; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab