Title:Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities
Volume: 20
Issue: 7
Author(s): Klara Gyires, Eva Viktoria Toth and Sandor Zoltan Zadori
Affiliation:
Keywords:
Inflammatory bowel disease, colitis, microbiota, pattern recognition receptors, pro-inflammatory cytokines.
Abstract: 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-α, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-γ
), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10,
IL-11, IFN-β-1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF,
KGF, TGF-β, 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.
