Interleukin 18
Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18 gene.[1][2] The protein encoded by this gene is a proinflammatory cytokine.
Function
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]
Age-related macular degeneration (AMD)
IL-18 acts as a guardian of eyesight by eliminating VEGF from the eye, thereby suppressing the production of damaging blood vessels behind the retina at the back of the eye. In pre-clinical models, IL-18 was administered intravenously, improving on the regular ocular injections of VEGF antibodies that is the standard of care.[7] AMD is one of the most common forms of blindness among the aging. The two forms of AMD are 'dry' (the majority of cases) and wet, which causes 90% of blindings. Wet AMD causes sub-retinal blood vessels to grow excessively, which causes almost immediate central blindness. Prior treatment options for wet AMD were limited to the condition's end stages.[7]
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. PMID 7477296.
- ↑ 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. PMID 9693051.
- ↑ "Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)".
- ↑ 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. PMID 19394601.
- ↑ Liu Z, Wang H, Xiao W, Wang C, Liu G, Hong T (October 2010). "Thyrocyte interleukin-18 expression is up-regulated by interferon-γ and may contribute to thyroid destruction in Hashimoto's thyroiditis". Int J Exp Pathol 91 (5): 420–5. doi:10.1111/j.1365-2613.2010.00715.x. PMC 3003839. PMID 20586818.
- ↑ Sutinen EM, Pirttilä T, Anderson G, Salminen A, Ojala JO (2012). "Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells". J Neuroinflammation 9: 199. doi:10.1186/1742-2094-9-199. PMC 3458954. PMID 22898493.
- 1 2 Doyle SL, Ozaki E, Brennan K, Humphries MM, Mulfaul K, Keaney J, Kenna PF, Maminishkis A, Kiang AS, Saunders SP, Hams E, Lavelle EC, Gardiner C, Fallon PG, Adamson P, Humphries P, Campbell M (2014). "IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration". Sci Transl Med 6 (230): 230ra44. doi:10.1126/scitranslmed.3007616. PMID 24695684. Lay summary – Medicalxpress.com.
Further reading
- 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. PMID 11894141.
- Nakanishi K (2002). "[Regulation of Th1 and Th2 immune responses by IL-18]". Kekkaku 77 (2): 87–93. PMID 11905033.
- Reddy P, Ferrara JL (2003). "Role of interleukin-18 in acute graft-vs-host disease". J. Lab. Clin. Med. 141 (6): 365–71. doi:10.1016/S0022-2143(03)00028-3. PMID 12819633.
- 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. PMID 14561165.
- 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. PMID 14640907.
- Yoshimoto T, Nakanishi K (2006). "Roles of IL-18 in basophils and mast cells". Allergology international : official journal of the Japanese Society of Allergology 55 (2): 105–13. doi:10.2332/allergolint.55.105. PMID 17075246.
- 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. PMID 17586702.
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