Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18gene.[1][2] The protein encoded by this gene is a proinflammatory cytokine.
IL-18 is a cytokine that belongs to the IL-1 superfamily and is produced by macrophages and other cells. IL-18 works by binding to the interleukin-18 receptor, and together with IL-12 it induces cell-mediated immunity following infection with microbial products like lipopolysaccharide (LPS). After stimulation with IL-18, natural killer (NK) cells and certain T cells release another important cytokine called interferon-γ (IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.
The combination of this cytokine and IL12 has been shown to inhibit IL-4 dependent IgE and IgG1 production, and enhance IgG2a production in B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine, and thus negatively regulate its biological activity.[3]
Clinical significance
Apart from its physiological role, IL-18 is also able to induce severe inflammatory reactions, which suggests its role in certain inflammatory disorders.
Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 are significantly increased in adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.[4]
IL-18 has been implicated as an inflammatory mediator of Hashimoto's thyroiditis, the most common cause of autoimmune hypothyroidism. IL-18 is up regulated by interferon-gamma.[5]
IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.[6]
References
↑Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K (November 1995). "Cloning of a new cytokine that induces IFN-gamma production by T cells". Nature. 378 (6552): 88–91. doi:10.1038/378088a0. PMID7477296.
↑Nolan KF, Greaves DR, Waldmann H (July 1998). "The human interleukin 18 gene IL18 maps to 11q22.2-q22.3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci". Genomics. 51 (1): 161–3. doi:10.1006/geno.1998.5336. PMID9693051.
↑Huang HY, Yu HT, Chan SH, Lee CL, Wang HS, Soong YK (June 2010). "Eutopic endometrial interleukin-18 system mRNA and protein expression at the level of endometrial-myometrial interface in adenomyosis patients". Fertil. Steril. 94 (1): 33–9. doi:10.1016/j.fertnstert.2009.01.132. PMID19394601.
Biet F, Locht C, Kremer L (2002). "Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens". J. Mol. Med. 80 (3): 147–62. doi:10.1007/s00109-001-0307-1. PMID11894141.
Nakanishi K (2002). "[Regulation of Th1 and Th2 immune responses by IL-18]". Kekkaku. 77 (2): 87–93. PMID11905033.
Kanai T, Uraushihara K, Totsuka T, et al. (2003). "Macrophage-derived IL-18 targeting for the treatment of Crohn's disease". Current drug targets. Inflammation and allergy. 2 (2): 131–6. doi:10.2174/1568010033484250. PMID14561165.
Matsui K, Tsutsui H, Nakanishi K (2005). "Pathophysiological roles for IL-18 in inflammatory arthritis". Expert Opin. Ther. Targets. 7 (6): 701–24. doi:10.1517/14728222.7.6.701. PMID14640907.
Yoshimoto T, Nakanishi K (2006). "Roles of IL-18 in basophils and mast cells". Allergology International. 55 (2): 105–13. doi:10.2332/allergolint.55.105. PMID17075246.
Orozco A, Gemmell E, Bickel M, Seymour GJ (2007). "Interleukin 18 and periodontal disease". J. Dent. Res. 86 (7): 586–93. doi:10.1177/154405910708600702. PMID17586702.
