Interleukin-23

Author:Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 02.10.2023

Dieser Artikel auf Deutsch

Synonym(s)

IL-12; IL-23; Interleukin 23

Requires free registration (medical professionals only)

Please login to access all articles, images, and functions.

Our content is available exclusively to medical professionals. If you have already registered, please login. If you haven't, you can register for free (medical professionals only).


Requires free registration (medical professionals only)

Please complete your registration to access all articles and images.

To gain access, you must complete your registration. You either haven't confirmed your e-mail address or we still need proof that you are a member of the medical profession.

Finish your registration now

DefinitionThis section has been translated automatically.

Interleukins (from Latin/Greek inter = between; leukos = white; kinein = to move) is the name given to a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL38). Interleukins are mediators for induction, progression, and control of T-cell-mediated cytotoxic immune responses as well as B-cell activation (antibody production). They are predominantly produced and secreted by stimulated leukocytes, monocytes and macrophages. To date, about 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatorically assigned a number for its classification (IL-1 to IL-38).

Some structurally related substances have been grouped into families. Their members often have a similar function or participate in the fine regulation of immune responses, for example, by regulating the synthesis of related interleukins.

Interleukin-23 (IL-23) is a heterodimeric, pleiotropic cytokine that belongs to the interleukin-12 family. The cytokine is composed of 2 subunits: the IL-12B subunit (this is identical to IL-12p40 a subunit of interleukin-12) and the IL23A subunit(IL-23p19). Interleukin-23 was discovered when experimental approaches revealed that another potent binding partner exists for the IL-12p40 subunit of interleukin-12.

General informationThis section has been translated automatically.

Interleukin-23, like interleukin-12, is mainly produced by B lymphocytes after induction, mainly by bacteria or bacterial components. To a lesser extent also by activated T cells, but also by subsets of dendritic cells (e.g. lamina propria dendritic cells - CD103+ u. CD11b+ LPDC) or by activated synovial fibroblasts.

Experimental studies on autoimmune encephalomyelitis showed Hyears ago that not interleukin-12 as originally assumed was responsible for the inflammatory reaction, but a then unknown interleukin, IL-23. Interleukin-23 also binds to the IL-12p40 subunit . Analogous study results in other models of inflammation, such as arthritis, inflammatory bowel disease, and psoriasis confirmed the hypothesis of dual use of the IL-12p40 subunit by interleukins-12 and -23.

Interleukin 23 binds to the interleukin-23 receptor. This has been identified and is composed of the IL-12R β1 receptor portion and the IL-23R receptor portion. IL23- functions can be considered part of the response of the innate and adaptive immune system to infection of peripheral tissues.

Interleukin-23 has an activating effect on the proliferation of T cells (T helper cells, Th-17 cells), NK cells, and possibly macrophages and osteoclasts. Upon binding to its receptor, there is activation of the JAK/STAT signaling cascade and triggering of phosphoinositide 3-kinase ( PI3K ) of RAC-alpha serine/threonine kinase (AKT) and NF-kappaB.

IL23 is jointly responsible for inflammatory processes in autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, psoriasis, Crohn's disease, nephritis in systemic lupus erythematosus. Furthermore, the cytokine plays a pathogenetic role in allergic bronchial asthma. Here it is responsible for the infiltration of the mucosa with neutrophil granulocytes. Interleukin-23 plays a role in tumor development by suppressing tumor-destructive effects of interleukin-12.

Interleukin-23 inhibitively regulates interleukin-10 production, but activates interleukin-12 and interleukin-17 production.

General therapyThis section has been translated automatically.

The human IgG antibody ustekinumab (as well as briakinumab) binds to the common p40 subunit of unbound IL-12 and -23 and inhibits their binding to the common receptor IL-12R on the surface of naïve T cells. Both cytokines promote T cell differentiation into mature Th1 and Th17 cells, respectively, and their release of TNF-α and IFN-γ. Ustekinumab inhibits T-cell differentiation and the release of proinflammatory cytokines and is highly effective in psoriasis and psoriatic arthritis.

Guselkumab, a fully humanized monoclonal antibody binds to interleukin-23 and proved superior to adalimumab in a randomized double-blind Phase III study (VOYAGE 2). The antibody is approved as an effective treatment option for moderate to severe psoriasis (Reich et al 2017).

Risankizumab, an interleukin-23 inhibitor in clinical trials. In 2 pivotal, randomized, placebo-controlled, double-blind trials (ultIMMa-1/ ultIMMa-2), the co-primary endpoints of improving PASI by 90 and >90%, respectively, were achieved in patients with moderate-to-severe psoriasis after 16 weeks of treatment with risankizumab (150mg). Response to risankizumab was significantly better compared to ustekinumab. This biologic also proved superior when compared to the TNF-alpha antagonist adalimumab.

Tildrakizumab: a humanized IgG1/k monoclonal antibody (produced in Chinese hamster ovary cells, CHO cells-) with anti-inflammatory and selective immunosuppressive activity. Tildrakizumab is used for the treatment of plaque psoriasis. The effects are also based on the binding and inactivation of interleukin-23 (IL-23); the antibody further inhibits its interaction with the IL-23 receptor.

LiteratureThis section has been translated automatically.

  1. Chan JR et al (2006) IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. Journal of Experimental Medicine 203: 2577-2587.
  2. Chan IH et al (2014) Interleukin-23 is sufficient to induce rapid de novo good tumorigenesis, independent of carcinogens, through activation of innate lymphoid cells. Mucosal Immunol 7:842-856.
  3. Cowardin CA et al(2015) Inflammasome activation contributes to interleukin-23 production in response to Clostridium difficile. MBio 6:1.
  4. Cua DJ et al (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421: 744-748.
  5. Kinnebrew MA et al.(2011) Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36:276-287.
  6. Murphy CA et al (2002) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. Journal of Experimental Medicine 198: 1951-1957.
  7. Li Y et al (2014) Mechanisms of pathogenesis in allergic asthma: role of interleukin-23. respirology 19:663-669.
  8. Reich K et al (2017) Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol 76:418-431.
  9. Rong C et al(2012) Interleukin-23 as a potential therapeutic target for rheumatoid arthritis. Mol Cell Biochem 361:243-248.
  10. Yen D et al(2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6 Journal of Clinical Investigation 116: 1310-1316.
  11. Xia LP et al(2015) Interleukin-27 and interleukin-23 in patients with systemic lupus erythematosus: possible role in lupus nephritis. Scand J Rheumatol 44:200-205.
  12. Yeremenko N et al (2014) The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis.Curr Opin Rheumatol 26:361-370.

Authors

Last updated on: 02.10.2023