Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 11:13:919973.
doi: 10.3389/fimmu.2022.919973. eCollection 2022.

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

Stella Amarachi Ihim  1   2   3 , Sharafudeen Dahiru Abubakar  4   5 , Zeineb Zian  6 , Takanori Sasaki  7   8 , Mohammad Saffarioun  9 , Shayan Maleknia  9 , Gholamreza Azizi  10
Affiliations
Review

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

Stella Amarachi Ihim et al. Front Immunol. .

Abstract

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine involved in host defense against infections and regulates the innate and acquired immune response. IL-18 is produced by both hematopoietic and non-hematopoietic cells, including monocytes, macrophages, keratinocytes and mesenchymal cell. IL-18 could potentially induce inflammatory and cytotoxic immune cell activities leading to autoimmunity. Its elevated levels have been reported in the blood of patients with some immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, type I diabetes mellitus, atopic dermatitis, psoriasis, and inflammatory bowel disease. In the present review, we aimed to summarize the biological properties of IL-18 and its pathological role in different autoimmune diseases. We also reported some monoclonal antibodies and drugs targeting IL-18. Most of these monoclonal antibodies and drugs have only produced partial effectiveness or complete ineffectiveness in vitro, in vivo and human studies. The ineffectiveness of these drugs targeting IL-18 may be largely due to the loophole caused by the involvement of other cytokines and proteins in the signaling pathway of many inflammatory diseases besides the involvement of IL-18. Combination drug therapies, that focus on IL-18 inhibition, in addition to other cytokines, are highly recommended to be considered as an important area of research that needs to be explored.

Keywords: autoimmune diseases; immunity; inflammatory diseases; interleukin-18; monoclonal antibodies.

PubMed Disclaimer

Conflict of interest statement

Authors MS and SM were employed by AryoGen Pharmed Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The cell sources and signaling mechanism for Interleukin 18.
See this image and copyright information in PMC

References

    1. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol (2010) 10(2):89–102. doi: 10.1038/nri2691 - DOI - PubMed
    1. Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, et al. . A new nomenclature for IL-1-family genes. Trends Immunol (2001) 22(10):536–7. doi: 10.1016/S1471-4906(01)02040-3 - DOI - PubMed
    1. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol (2001) 19:423–74. doi: 10.1146/annurev.immunol.19.1.423 - DOI - PubMed
    1. Nakanishi K. Unique action of interleukin-18 on t cells and other immune cells. Front Immunol (2018) 9:763. doi: 10.3389/fimmu.2018.00763 - DOI - PMC - PubMed
    1. Yasuda K, Nakanishi K, Tsutsui H. Interleukin-18 in health and disease. Int J Mol Sci (2019) 20(3):649–701. doi: 10.3390/ijms20030649 - DOI - PMC - PubMed