Impact of infliximab on serum leptin levels in patients with Crohn's disease
Impact of infliximab on serum leptin levels in patients with Crohn's disease
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DOI：
10.1210/jc.2004-1222
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发表时间：
2005-06-01
影响因子：
5.8
通讯作者：
Van Gossum, A
中科院分区：
文献类型：
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作者：
Franchimont, D;Roland, S;Van Gossum, A
目的：小鼠体重受脂肪细胞源性瘦素调节。TNF α是炎症诱导的克罗恩病（CD）恶病质的关键介质。在CD患者中，TNF α对瘦素的调节尚不清楚。英夫利昔单抗对TNF α的药理中和为研究TNF α介导的CD患者瘦素调节提供了一个独特的机会。方法：对20例接受英夫利昔单抗治疗的乳糜泻患者进行前瞻性随访。在治疗前和治疗后第1周和第4周评估体成分。测定血清瘦素、IL-6、可溶性TNF受体II型和可溶性细胞间抗粘附分子-1水平，以及胆固醇水平和游离尿皮质醇水平。由于甲基强的松龙（methylprednisolone， MP）可增加体内瘦素的产生，因此将接受MP治疗的CD患者（n = 9）作为阳性对照组单独进行研究。结果：英夫利昔单抗诱导临床缓解，4周时所有CD患者c反应蛋白（P < 0.01）和IL-6水平显著降低（P < 0.05），体重增加（P = 0.013）。给予英夫利昔单抗后1周和4周瘦素血症显著升高（P = 0.014）。血清瘦素的增加发生在第1周早期，此时没有观察到明显的体重和脂肪量变化，并且与TNF α调节的介质，可溶性TNF受体II型（P = 0.015）和可溶性细胞间抗粘附分子-1 （P = 0.007）的下调有关。此外，英夫利昔单抗在1周时增加了胆固醇水平（P = 0.001）。英夫利昔单抗未改变24小时皮质醇分泌。给药后1周瘦素水平升高（P = 0.028）。结论：英夫利昔单抗增加CD患者瘦素血症。本研究提示TNF α对CD患者瘦素产生有主要抑制作用。
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.