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

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