Anti-TNF Monoclonal antibody, clone 22 [PerCP/Cy5.5®]

Background Infliximab (IFX) is used in active Crohn's disease for induction and maintenance of remission. There are scanty data on weight gain in IBD-patients under anti-TNF treatment. We investigated changes in weight and blood chemistry in anti-TNF-naive Crohn's disease patients during their first course of IFX. Methods Retrospective analysis of 110 patients (77 men, 33 women) aged 34 years (range 14-73), 54 with luminal and 56 with fistulising disease, given at least 3 infusions of IFX (range 3-11). Data regarding body weight, height, C-reactive protein (CRP), haemoglobin and S-albumin at baseline, before the third infusion, at three months and at 12 months were collected. Results At 6 weeks, 65 (59%) increased in weight, 73% and 76% at three and 12 months, respectively. There was an increase in median weight (1.7 kg, IQR = 3.1 kg) and BMI (0.5 kg/m(2), IQR = 1.2 kg/m(2)) at 6 weeks, which persisted at three and 12 months (all p < .001). There was no difference between men and women. Young patients, patients with underweight or fistulising disease increased most in weight. Disease activity assessed by PGA and SES-CD decreased at all time points (p < .05). Increases in weight and BMI correlated with an increase in serum albumin and a decrease in CRP. Conclusion Approximately 60% of Crohn's disease patients experience weight gain within the first six weeks of infliximab treatment. The weight increment correlates with improvements in inflammatory markers and disease activity. The causes of weight gain may be related to treatment induced metabolic changes and reduced inflammatory burden.

Overweight and obesity are accompanied by insulin resistance, impaired intestinal barrier function resulting in increased lipopolysaccharide (LPS) levels, and a low-grade chronic inflammation that results in macrophage activation. Macrophages produce a range of interleukins as well as prostaglandin E-2 (PGE(2)). To cope with insulin resistance, hyperinsulinemia develops. The purpose of the study was to elucidate how LPS, insulin and PGE(2) might interact to modulate the inflammatory response in macrophages. Human macrophages were either derived by differentiation from U937 cells or isolated from blood mononuclear cells. The macrophages were stimulated with LPS, insulin and PGE(2). Insulin significantly enhanced the LPS-dependent expression of interleukin-1 beta and interleukin-8 on both the mRNA and protein levels. Additionally, insulin increased the LPS-dependent induction of enzymes involved in the PGE(2)-synthesis and the production of PGE(2) by macrophages. PGE(2) in turn further enhanced the LPS-dependent expression of cytokines via its G(s)-coupled receptors EP2 and EP4, the latter of which appeared to be more relevant. The combination of all three stimuli resulted in an even higher induction than the combination of LPS plus insulin or LPS plus PGE(2). Thus, the compensatory hyperinsulinemia might directly and indirectly enhance the LPS-dependent cytokine production in obese individuals.