Original article 283 Effects of tumor necrosis factor alpha inhibition with infliximab on lipid levels and insulin resistance in patients with inflammatory bowel disease Ioannis E. Koutroubakis a , Pantelis Oustamanolakis a , Niki Malliaraki d , Konstantinos Karmiris a , Ioannis Chalkiadakis a , Emmanouel Ganotakis b , Nikolaos Karkavitsas c and Elias A. Kouroumalis a Introduction TNF-a is a critical mediator of inflammation with an important role in metabolic profile and insulin resistance. The regulation of these parameters by TNF-a in inflammatory bowel disease (IBD) is, however, poorly understood. The aim of this study was to assess the in-vivo TNF-a-mediated regulation of insulin resistance and of lipid levels in patients with IBD. Methods Twenty-two patients with IBD (eight females; 19 Crohn’s disease) received infliximab according to treating physician’s assessment at weeks 0, 2 and 6 from baseline and subsequently every 8 weeks and were prospectively followed for 14 weeks. Fasting insulin, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A1 (apo-A1), apolipoprotein B100 and lipoprotein a were measured in serum at baseline and at week 14. Insulin resistance was calculated with the use of the Homeostasis Model Assessment index. Results Infliximab therapy induced clinical response or remission in 19 of the 22 patients. C-reactive protein levels were significantly decreased by week 14. Body mass index was increased in all patients. No difference was observed in insulin levels, Homeostasis Model Assessment index, triglycerides, LDL cholesterol, apolipoprotein B100 and lipoprotein a. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels were significantly increased from baseline. Conclusion TNF-a inhibition does not alter insulin resistance in IBD patients. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels are significantly increased after infliximab treatment compared with baseline. The importance of these alterations needs to be clarified in future studies. Eur J Gastroenterol Hepatol 21:283–288  c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2009, 21:283–288 Keywords: cholesterol, Crohn’s disease, infliximab, insulin resistance, ulcerative colitis Departments of a Gastroenterology, b Internal Medicine, c Nuclear Medicine, and d Laboratories of Biochemistry, University Hospital Heraklion, Crete, Greece Correspondence to Ioannis E. Koutroubakis, MD, PhD, Assistant Professor of Medicine, Department of Gastroenterology, University Hospital Heraklion, PO Box 1352, Heraklion 71110, Crete, Greece Tel: + 30 2810 392253; fax: + 30 2810 542085; e-mail: ikoutroub@med.uoc.gr Received 6 November 2008 Accepted 9 December 2008 Introduction Inflammatory bowel disease (IBD) is known for years to be associated with an increased risk of vascular complications [1,2]. An increased atherosclerotic risk in patients with IBD has also been reported [3]. It could be suggested that proinflammatory cytokines produced by the inflamed intestine can diffuse within the blood- stream, where they may alter the function of numerous tissues including fat and the vascular endothelium [2,4]. These functional alterations can induce changes, such as insulin resistance, increased oxidative stress, endothelial dysfunction and dyslipidemia that promote atherogenesis. Insulin resistance is an established risk factor for cardiovascular disease and constitutes a central mechan- ism in the metabolic syndrome, wherein it clusters particularly with dyslipidemia and impaired glucose metabolism [5]. Most of the adipokines, which are cytokines and hormones with metabolic and immune- modulating properties, have been found associated with insulin resistance [6]. Over-expression of adipokines such as leptin, adiponectin and resistin in mesenteric adipose tissue of patients with Crohn’s disease (CD) and significant alterations of circulating serum levels of these adipokines in IBD have been reported [7–9]. Increased insulin resistance has also been recently reported in a series of 17 patients with CD [10]. TNF-a is a critical mediator of inflammation. TNF-a has been shown to have important effects on insulin sensitivity and glucose metabolism [11]. TNF-a neutra- lization ameliorates vascular reactivity in the metabolic syndrome during hyperinsulinemia, probably because of decreased oxidative stress [12]. Infliximab (IFX) is a 0954-691X  c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MEG.0b013e328325d42b Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.