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Salivary Levels of Interleukin-23 in Iranian Patients with Systemic Sclerosis

Document Type : Original Article

Authors

1 Department of Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 Undergraduate Student, Department of Oral and Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

5 Oral and Dental Disease Research Center, Department of Oral and Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Systemic sclerosis (SSc) is a rare chronic inflammatory disorder characterized by diffuse fibrosis and vascular abnormalities in the skin and internal organs. Interleukin-23 (IL-23) is a pro-inflammatory cytokine that can enhance the expansion of T helper 17 (Th17) cells and thus plays a critical role in many inflammatory autoimmune diseases. This study aimed to assess the salivary IL-23 levels in Iranian patients with SSc compared to healthy individuals.
Methods: In this cross-sectional study, unstimulated saliva samples (5 cc) were collected from 88 SSc patients and 88 age- and sex-matched healthy individuals. The salivary levels of IL-23 in the saliva samples were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit.
Results: The mean salivary levels of IL-23 in the patient group were significantly higher than in the control subjects (164.5 ± 22.1 ng/L vs. 95.8 ± 15.7 ng/L, P < 0.0001). In SSc patients, the salivary IL-23 levels were significantly elevated in ACA-positive compared to ACA-negative participants (179.8 ± 11.2 ng/L vs. 144.3 ± 15.7 ng/L, P < 0.0001). However, IL-23 was not associated with gender or age (P > 0.05).
Conclusion: The results suggest that IL-23 is associated with the pathogenesis of SSc; therefore, this pro-inflammatory cytokine is not only a valuable supportive biomarker for monitoring the disease progression but also blocking IL-23 could be considered a potential therapeutic target, especially in early SSc. Further comprehensive studies are needed to confirm our findings.

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References
  1. Hashempour A, Moayedi J, Musavi Z, Ghasabi F, Halaji M, Hasanshahi Z, et al. First report of HHV-8 viral load and seroprevalence of major blood-borne viruses in Iranian patients with systemic sclerosis. Mult Scler Relat Disord. 2021;51:102872. doi: 10.1016/j.msard.2021.102872.
  2. Fuschiotti P. Current perspectives on the immunopathogenesis of systemic sclerosis. Immunotargets Ther. 2016;5:21-35. doi: 10.2147/itt.s82037.
  3. Sierra-Sepúlveda A, Esquinca-González A, Benavides-Suárez SA, Sordo-Lima DE, Caballero-Islas AE, Cabral-Castañeda AR, et al. Systemic sclerosis pathogenesis and emerging therapies, beyond the fibroblast. Biomed Res Int. 2019;2019:4569826. doi: 10.1155/2019/4569826.
  4. Stern EP, Denton CP. The pathogenesis of systemic sclerosis. Rheum Dis Clin North Am. 2015;41(3):367-82. doi: 10.1016/j. rdc.2015.04.002.
  5. Barnes J, Mayes MD. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol. 2012;24(2):165- 70. doi: 10.1097/BOR.0b013e32834ff2e8.
  6. Coondoo A. The role of cytokines in the pathomechanism of cutaneous disorders. Indian J Dermatol. 2012;57(2):90-6. doi: 10.4103/0019-5154.94272.
  7. Liu T, Li S, Ying S, Tang S, Ding Y, Li Y, et al. The IL-23/IL- 17 pathway in inflammatory skin diseases: from bench to bedside. Front Immunol. 2020;11:594735. doi: 10.3389/ fimmu.2020.594735.
  8. Yang X, Yang J, Xing X, Wan L, Li M. Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction. Arthritis Res Ther. 2014;16(1):R4. doi: 10.1186/ar4430.
  9. Truchetet ME, Brembilla NC, Chizzolini C. Current concepts on the pathogenesis of systemic sclerosis. Clin Rev Allergy Immunol. 2023;64(3):262-83. doi: 10.1007/s12016-021- 08889-8.
  10. Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and cancer. Ann Afr Med. 2019;18(3):121- 6. doi: 10.4103/aam.aam_56_18.
  11. Wu B, Sodji QH, Oyelere AK. Inflammation, fibrosis and cancer: mechanisms, therapeutic options and challenges. Cancers (Basel). 2022;14(3):552. doi: 10.3390/cancers14030552.
  12. Demir C, Şahin A, Küçükşahin O, Turgay T, Türkçapar N, Erten Ş, et al. Comparison of serum IL-23 and IL-17 levels in patients with systemic sclerosis and healthy subjects. J Clin Anal Med. 2015;6(1):83-7. doi: 10.4328/jcam.1709.
  13. Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006;116(5):1310-6. doi: 10.1172/jci21404.
  14. Qu N, Xu M, Mizoguchi I, Furusawa J, Kaneko K, Watanabe K, et al. Pivotal roles of T-helper 17-related cytokines, IL-17, IL- 22, and IL-23, in inflammatory diseases. Clin Dev Immunol. 2013;2013:968549. doi: 10.1155/2013/968549.
  15. Lu R, Zeng X, Han Q, Lin M, Long L, Dan H, et al. Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the lesions of oral lichen planus. Mediators Inflamm. 2014;2014:701094. doi: 10.1155/2014/701094.
  16. O’Reilly S, Hügle T, van Laar JM. T cells in systemic sclerosis: a reappraisal. Rheumatology (Oxford). 2012;51(9):1540-9. doi: 10.1093/rheumatology/kes090.
  17. Radstake TR, van Bon L, Broen J, Hussiani A, Hesselstrand R, Wuttge DM, et al. The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes. PLoS One. 2009;4(6):e5903. doi: 10.1371/journal.pone.0005903.
  18. Komura K, Fujimoto M, Hasegawa M, Ogawa F, Hara T, Muroi E, et al. Increased serum interleukin-23 in patients with systemic sclerosis. J Rheumatol. 2008;35(1):120-5.
  19. Hammad GA, Eltanawy RM, Fawzy RM, Gouda TMA, Eltohamy MA. Serum interleukin-23 and its associations with interstitial lung disease and clinical manifestations of scleroderma. Egypt J Bronchol. 2018;12(1):69-75. doi: 10.4103/ejb.ejb_22_17.
  20. Gourh P, Arnett FC, Assassi S, Tan FK, Huang M, Diekman L, et al. Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations. Arthritis Res Ther. 2009;11(5):R147. doi: 10.1186/ar2821.
  21. Olewicz-Gawlik A, Danczak-Pazdrowska A, Kuznar- Kaminska B, Gornowicz-Porowska J, Katulska K, Trzybulska D, et al. Interleukin-17 and interleukin-23: importance in the pathogenesis of lung impairment in patients with systemic sclerosis. Int J Rheum Dis. 2014;17(6):664-70. doi: 10.1111/1756-185x.12290.
  22. Stritesky GL, Yeh N, Kaplan MH. IL-23 promotes maintenance but not commitment to the Th17 lineage. J Immunol. 2008;181(9):5948-55. doi: 10.4049/jimmunol.181.9.5948.
  23. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235-8. doi: 10.1038/nature04753.
  24. Nakayama W, Jinnin M, Tomizawa Y, Nakamura K, Kudo H, Inoue K, et al. Dysregulated interleukin-23 signalling contributes to the increased collagen production in scleroderma fibroblasts via balancing microRNA expression. Rheumatology (Oxford). 2017;56(1):145-55. doi: 10.1093/ rheumatology/kew336.
  25. Stamp LK, Easson A, Pettersson L, Highton J, Hessian PA. Monocyte derived interleukin (IL)-23 is an important determinant of synovial IL-17A expression in rheumatoid arthritis. J Rheumatol. 2009;36(11):2403-8. doi: 10.3899/ jrheum.081304.
  26. Fransen K, van Sommeren S, Westra HJ, Veenstra M, Lamberts LE, Modderman R, et al. Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway analysis in inflammatory bowel disease. Inflamm Bowel Dis. 2014;20(5):777-82. doi: 10.1097/mib.0000000000000013.
  27. Hollis-Moffatt JE, Merriman ME, Rodger RA, Rowley KA, Chapman PT, Dalbeth N, et al. Evidence for association of an interleukin-23 receptor variant independent of the R381Q variant with rheumatoid arthritis. Ann Rheum Dis. 2009;68(8):1340-4. doi: 10.1136/ard.2008.090142.
  28. Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171(11):6173-7. doi: 10.4049/ jimmunol.171.11.6173.
  29. McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23- IL-17 immune pathway. Trends Immunol. 2006;27(1):17-23. doi: 10.1016/j.it.2005.10.003.
  30. Nguyen CQ, Hu MH, Li Y, Stewart C, Peck AB. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjögren’s syndrome: findings in humans and mice. Arthritis Rheum. 2008;58(3):734-43. doi: 10.1002/art.23214.
  31. Toussirot E. The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm Allergy Drug Targets. 2012;11(2):159-68. doi: 10.2174/187152812800392805.
  32. Ratsimandresy RA, Duvallet E, Assier E, Semerano L, Delavallée L, Bessis N, et al. Active immunization against IL-23p19 improves experimental arthritis. Vaccine. 2011;29(50):9329- 36. doi: 10.1016/j.vaccine.2011.09.134.
  33. Najafi S, Mardani M, Motamedifar M, Nazarinia MA, Hadadi M. Salivary Streptococcus mutans and Lactobacilli levels as indicators of dental caries development in Iranian patients with systemic sclerosis. Iran J Med Microbiol. 2022;16(4):350- 6. doi: 10.30699/ijmm.16.4.350.
  34. Abbas MJ, Al Rawi NA, Al-Duboni GI. The role of salivary interleukin-17 as a dependent positive predictive biomarker among Iraqi patients with oral squamous cell carcinoma. J Pharm Sci Res. 2018;10(12):3149-52.
  35. Saheb Sharif-Askari F, Saheb Sharif-Askari N, Hafezi S, Mdkhana B, Alsayed HA, Ansari AW, et al. Interleukin-17, a salivary biomarker for COVID-19 severity. PLoS One. 2022;17(9):e0274841. doi: 10.1371/journal.pone.0274841.
  36. Parat K, Radić M, Perković D, Lukenda DB, Kaliterna DM. Reduced salivary flow and caries status are correlated with disease activity and severity in patients with diffuse cutaneous systemic sclerosis. J Int Med Res. 2020;48(10):300060520941375. doi: 10.1177/0300060520941375.
  37. Zian Z, Bakkach J, Barakat A, Ghailani Nourouti N, Bennani Mechita M. Salivary biomarkers in systemic sclerosis disease. Biomed Res Int. 2018;2018:3921247. doi: 10.1155/2018/3921247

 

Journal of Kerman University of Medical Sciences
Volume 31, Issue 3
May and June 2024
Pages 148-152
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