The pathogenesis and treatment of inflammatory bowel disease (IBD) have been

The pathogenesis and treatment of inflammatory bowel disease (IBD) have been recently advanced, while it is still challenged with high morbidity and poor prognosis. amelioration and remission of immune responses. The mechanisms of infliximab treatment for IBD were intensively discussed. The recent advances on two topics including predictors and side effects of infliximab treatment were also reviewed. 1. Introduction Inflammatory bowel disease (IBD), mainly containing Crohn’s disease (CD) and ulcerative colitis (UC), is a group of chronic inflammatory disorders in the colon and small intestine. Although the etiology of IBD remains unclear, the pathogenesis of IBD has been recently advanced. It is strongly suggested that altered immunological function, resulting from an interplay between genetic susceptibility and certain environmental factors including bacteria infection, contributes to the development of mucosal inflammatory responses of gastrointestinal tract [1]. Proinflammatory cytokines, especially tumor necrosis factor (TNF), are produced mainly by activated immune cells in inflamed mucosa during the process of IBD, and those proinflammatory cytokines further activate immune cells, as the feedback, to produce toxic molecules including super oxygen products, chemokines, proteinases, and cytokines which result in tissue damage and inflammation development [2, 3]. In the past years, TNF has been known to play a pivotal role in the pathogenesis of IBD [4]. When released by active macrophages and T lymphocytes, TNF initiates multiple biological reactions below: modulates immune cell function, drives adaptive immune responses, triggers epithelium apoptosis Emodin and breaks epithelial barrier, induces endothelium expressing adhesion molecules such as intercellular adhesion molecule 1 (ICAM1) to recruit immune cells, and regulates matrix metalloproteinase (MMP) expression to induce tissue degradation and damage [5, 6]. Clinical studies have shown that TNF protein and mRNA levels are elevated in serum, intestinal tissue, stool of active IBD, in correlation with disease activity [4, 7C9]. Clinical inhibition of TNF production has been linked with disease remission, improved life quality, and relapse prevention, meanwhile, failure of clinical treatment of IBD has been attributed to early reactivation of TNF secretory capacity by immune cells [10, 11]. The findings suggest that TNF is Emodin critical for disease development. Inhibiting TNF production in inflamed mucosa is one of the important goals for IBD management. The conventional treatments of IBD include corticosteroids and aminosalicylates. However, only 50% of patients achieve sustained remission with the conventional drugs which can raise many side effects [12]. Recently, many novel drugs have been developed for clinical IBD management, and among them, TNF neutralization by monoclonal antibodies has been shown as one of the effective approaches for IBD treatment [13]. 1.1. TNF and Infliximab TNF is primarily a type II transmembrane protein with 212 amino acid sequence and exists in a stable homotrimer. TNF alpha converting enzyme (TACE) is a metalloprotease which can cleave membrane-integrated TNF and release TNF in a soluble homotrimeric form [4, 9]. Both membrane and soluble TNF can perform their biological Ntrk3 function by binding to their Emodin receptors including receptor 1 (TNFR1, CD120a) and TNFR2 (CD120b), which are expressed by most tissue cells. Through its receptor TNFR1, TNF can activate intracellular pathways including transcription factor nuclear factor-< 0.001 for the comparison of Emodin the cA2 group as a whole with placebo). 33% patients given cA2 went into remission, as compared with 4% of the patients given placebo (= 0.005). At 12 weeks, 34 of 83 cA2-treated patients had had a clinical response, as compared with 3 of 25 patients in the placebo group (= 0.008). Infliximab for Crohn's disease remission maintenance was also reported [51]. Besides clinical use for intestinal inflammation, infliximab has currently been authorized for another two phenotypes of active Crohn's disease: stricturing disease (which causes narrowing of the bowel) and penetrating disease (which causes fistulae or abnormal connections of the bowel) [52C54]. In a multicenter, double-blind, randomized, placebo-controlled trial [55], 306 Crohn's disease patients with one or more draining abdominal or perianal fistulas of Emodin at least three months' duration received infliximab (5?mg/kg) intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or infliximab every eight weeks and to be followed to week 54. The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks versus 14 weeks, < 0.001). At week 54, 19 percent of individuals in the placebo maintenance group experienced a complete absence of draining fistulas, as compared with 36 percent of individuals in the infliximab maintenance group (= 0.009). As demonstrated by this and additional tests, infliximab was effective in short-term closure of rectovaginal fistulas and maintenance treatment was more effective than placebo in prolonging rectovaginal fistula closure. Clinical effectiveness of infliximab on ulcerative colitis has been clarified. Many medical trials evaluated.