Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

被引:39
作者
Gyires, Klara [1 ]
Toth, Eva Viktoria [1 ]
Zadori, Sandor Zoltan [1 ]
机构
[1] Semmelweis Univ, Fac Med, Dept Pharmacol & Pharmacotherapy, H-1089 Budapest, Hungary
关键词
Inflammatory bowel disease; colitis; microbiota; pattern recognition receptors; pro-inflammatory cytokines; TUMOR-NECROSIS-FACTOR; MIGRATION-INHIBITORY FACTOR; ACTIVE ULCERATIVE-COLITIS; GENOME-WIDE ASSOCIATION; COLONY-STIMULATING FACTOR; EPIDERMAL-GROWTH-FACTOR; INVASIVE ESCHERICHIA-COLI; SODIUM-INDUCED COLITIS; TOLL-LIKE RECEPTOR-4; NOD-LIKE RECEPTORS;
D O I
10.2174/13816128113199990417
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e. g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-gamma), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN-beta-1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-beta, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.
引用
收藏
页码:1063 / 1081
页数:19
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