Modulation of IL-12/IL-23 signaling pathways by ustekinumab alleviates inflammation in Crohn’s disease patients

Authors: J. Krejsek
Authors‘ workplace: Ústav klinické imunologie a alergologie, LF UK a FN Hradec Králové
Published in: Gastroent Hepatol 2018; 72(4): 334-339
doi: 10.14735/amg2018334


Crohn’s disease (CD) is a multifactorial illness, in which pathogenesis involving damage to the inflammatory response, mediated by abnormally polarized Th1 and Th17 subsets of T cell, is a prominent feature. CD treatment options employing biological therapies, predominantly based on antitumor necrosis factor α biologics, are limited compared with other immunological diseases. With the exception of vedolizumab among numerous other biologics tested so far, clinical efficacy has recently been approved only for ustekinumab, which targets subunit p40 shared by both IL-12 and IL-23 interleukins. Interleukin-12 is indispensable for the functional polarization of T cells into the Th1 subset. Interleukin-23 is essential for the full activation and survival of the Th17 subset of T cells. Immunomodulatory intervention employing targeting of IL-12/IL-23 signaling pathways via ustekinumab alleviates inflammatory reactions in patients with CD. In addition, ustekinumab treatment is not associated with an increased risk of immunity impairment or decreased protective and barrier function of gut mucosa, which are common side effects of other biologics, especially those targeting IL-17/IL-17R signaling pathways. The clinical efficacy of another treatment targeting the unique subunit of p19 of IL-23 in CD patients is now being tested in ongoing clinical trials.

Key words:

Crohn’s disease – inflammation – Th1/Th17 subsets – signaling pathway IL-12/IL-23 – biological therapy – ustekinumab

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted: 4. 6. 2018

Accepted: 4. 7. 2018 


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