Gut inflammation: Current update on pathophysiology, molecular mechanism and pharmacological treatment modalities

K. Gyires, Éva Viktória Tóth, Z. Zádori

Research output: Contribution to journalArticle

30 Citations (Scopus)

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-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN-1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, 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.

Original languageEnglish
Pages (from-to)1063-1081
Number of pages19
JournalCurrent Pharmaceutical Design
Volume20
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

Inflammatory Bowel Diseases
Pharmacology
Inflammation
Cytokines
Interleukin-11
Anti-Bacterial Agents
Interleukin-23
Mucosal Immunity
Interleukin-18
Interleukin-13
Interleukin-17
Helminths
Probiotics
Granulocyte Colony-Stimulating Factor
Therapeutics
Genetic Predisposition to Disease
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Biological Products
Hygiene

Keywords

  • Colitis
  • Inflammatory bowel disease
  • Microbiota
  • Pattern recognition receptors
  • Pro-inflammatory cytokines

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

Cite this

Gut inflammation : Current update on pathophysiology, molecular mechanism and pharmacological treatment modalities. / Gyires, K.; Tóth, Éva Viktória; Zádori, Z.

In: Current Pharmaceutical Design, Vol. 20, No. 7, 2014, p. 1063-1081.

Research output: Contribution to journalArticle

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