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Review
. 2020 Nov 26:9:289-297.
doi: 10.2147/ITT.S282466. eCollection 2020.

All are Equal, Some are More Equal: Targeting IL 12 and 23 in IBD - A Clinical Perspective

André Jefremow  1   2 , Markus F Neurath  1   2
Affiliations
Review

All are Equal, Some are More Equal: Targeting IL 12 and 23 in IBD - A Clinical Perspective

André Jefremow et al. Immunotargets Ther. .

Abstract

Chronic inflammatory diseases like inflammatory bowel diseases (IBD) or psoriasis represents a worldwide health burden. Researchers provided great achievements in understanding the origin of these diseases leading to improved therapeutic options. The discovery of cytokines like tumor necrosis factor-α or transforming growth factor-β are examples for these efforts. Interleukin 12 (IL 12) and interleukin 23 (IL 23) represent different important cytokines in this regard. They both belong to the interleukin 12 family and are related by sharing the subunit p40. Ustekinumab is an antibody that blocks p40 and thereby interleukins 12 and 23. Trials showed promising results in treating IBD patients with this drug. Consequently, new questions arose about the distinct features of IL 12 and 23. This review focuses on these interleukins regarding their functions in the healthy and inflamed gut and provides an overview about the results from in vitro and in vivo studies as well as clinical trials.

Keywords: Crohn’s disease; inflammatory bowel diseases; interleukin 12; interleukin 23; ulcerative colitis.

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Conflict of interest statement

Markus Neurath declares personal fees from Boehringer & Abbvie, from Roche & Takeda, and from J&J, during the conduct of the study. André Jefremow declares speaker fees from AbbVie, MSD, and Eisai, traveller grants from Servier and Amgen, Sponsoring from Amgen, Cellgene, and Lilly, and personal fees from Servier und Amgen. The authors report no other potential conflicts of interest for this work.

Figures

Figure 1
Figure 1
The interleukin 12 family: IL 12, IL 23, IL 27, and IL 35 are composed out of the α-subunits p19, p28, and p35 and the β-subunits p40 and EBI3. They interact with their different receptors and receptor chains. Created with Biorender.com.
Figure 2
Figure 2
Macrophages produce IL 23 leading to production of anti-inflammatory cytokines like IL 10 and TGF-β under healthy conditions in the small intestine. Created with BioRender.com.
Figure 3
Figure 3
In the context of inflammation macrophages and monocytes stimulate production IL 12 and IL 23 in the large intestine. While IL 12 provides a Th 1 response, IL 23 is responsible for a Th17 response. Consequently, T cells produce proinflammatory cytokines like TNF-α and IFN-γ. Created with Biorender.com.
See this image and copyright information in PMC

References

    1. Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365(18):1713–1725. - PubMed
    1. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389(10080):1741–1755. doi:10.1016/S0140-6736(16)31711-1 - DOI - PubMed
    1. Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011;140(6):1807–1816. - PubMed
    1. Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–2114.e5. doi:10.1053/j.gastro.2010.01.058 - DOI - PubMed
    1. Neurath MF. IL-23: a master regulator in Crohn disease. Nat Med. 2007;13(1):26–27. - PubMed

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