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Impact of infliximab on serum leptin levels in patients with Crohn's disease.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2005 Jun; Vol. 90 (6), pp. 3510-6. Date of Electronic Publication: 2005 Mar 22. - Publication Year :
- 2005
-
Abstract
- 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.<br />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.<br />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).<br />Conclusion: Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.
- Subjects :
- Adult
Biomarkers blood
Body Mass Index
Female
Humans
Infliximab
Interleukin-6 blood
Male
Receptors, Leptin
Receptors, Tumor Necrosis Factor, Type II blood
Regression Analysis
Tumor Necrosis Factor-alpha physiology
Weight Gain drug effects
Antibodies, Monoclonal therapeutic use
Crohn Disease blood
Crohn Disease drug therapy
Leptin blood
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 90
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 15784704
- Full Text :
- https://doi.org/10.1210/jc.2004-1222