Association of Serum IL-17 and IL-23 Cytokines With Disease Activity and Various Parameters of Rheumatoid Arthritis in Indian Patients

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2024 Jan 1

PMID 38161845

Authors

Jhasaketan Meher

Suprava Patel

Rachita Nanda

Md Sabah Siddiqui

Affiliations

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Abstract

Introduction Interleukin-23/T helper 17 (IL-23/Th17) axis cytokine has been thought to be a critical pathway for rheumatoid arthritis (RA) disease development and its association with disease severity, joint erosion, and functional outcome. There is a paucity of data on the role of IL-23/Th17 axis cytokines in an Indian RA subset of patients. We aimed to determine the association between serum cytokines (interleukin-17 [IL-17] and [IL-23]) and disease activity as well as with clinical and biochemical parameters of RA patients. Methods In this observational cross-sectional study, 84 consecutive RA cases were recruited after obtaining consent. Serum IL-17 and IL-23 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. Clinical and laboratory parameters, disease activity score 28-erythocyte sedimentation rate (DAS28-ESR), and Health Assessment Questionnaire-II (HAQ-II) were recorded. Correlation of cytokines with various clinical and biochemical parameters was elicited. Results Only C-reactive protein (CRP) correlated positively with IL-23 (rs = 0.26, p = 0.014) but not the ESR. Both IL-17 and IL-23 levels showed an insignificant, weak positive correlation with the disease activity DAS28 (rs = 0.18, p = 0.097; rs = 0.12, p = 0.259, respectively). Neither IL-17 nor IL-23 levels differed among the disease severity group (p = 0.13, p = 0.215). Only the IL-23 level positively correlated with functional status (HAQ-II) (rs = 0.28, p = 0.009). IL-17 level was higher in advanced RA as compared to early RA (p = 0.028). Both IL-17 and IL-23 levels did not vary within the different subgroups (age, obesity, disease-modifying drugs/steroid/biologics use, and serology status). Conclusion Females had higher IL-23 levels than males. Advanced RA had higher IL-17 levels than early RA. The cytokine levels were not influenced by factors like age, duration of disease, serology status, or drugs. Neither of the cytokines correlated significantly with disease severity. Higher IL-17 levels may have a role in the progression of early non-erosive to chronic erosive arthritis. Higher IL-23 levels may signal a bad functional outcome.

References

Niu X, Chen G . Clinical biomarkers and pathogenic-related cytokines in rheumatoid arthritis. J Immunol Res. 2014; 2014:698192. PMC: 4158303. DOI: 10.1155/2014/698192. View

Rasmussen T, Andersen T, Hvid M, Hetland M, Horslev-Petersen K, Stengaard-Pedersen K . Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis. J Rheumatol. 2010; 37(10):2014-20. DOI: 10.3899/jrheum.100259. View

Stamp L, Easson A, Pettersson L, Highton J, Hessian P . 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. View

Schinocca C, Rizzo C, Fasano S, Grasso G, Barbera L, Ciccia F . Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview. Front Immunol. 2021; 12:637829. PMC: 7937623. DOI: 10.3389/fimmu.2021.637829. View

Millier M, Fanning N, Frampton C, Stamp L, Hessian P . Plasma interleukin-23 and circulating IL-17AIFNγ ex-Th17 cells predict opposing outcomes of anti-TNF therapy in rheumatoid arthritis. Arthritis Res Ther. 2022; 24(1):57. PMC: 8881822. DOI: 10.1186/s13075-022-02748-3. View

Wolfe F, Michaud K, Pincus T . Development and validation of the health assessment questionnaire II: a revised version of the health assessment questionnaire. Arthritis Rheum. 2004; 50(10):3296-305. DOI: 10.1002/art.20549. View

Scott D, Wolfe F, Huizinga T . Rheumatoid arthritis. Lancet. 2010; 376(9746):1094-108. DOI: 10.1016/S0140-6736(10)60826-4. View

Abu Al Fadl E, Fattouh M, Allam A . High IL-23 level is a marker of disease activity in rheumatoid arthritis. Egypt J Immunol. 2014; 20(2):85-92. View

Raza K, Scheel-Toellner D, Lee C, Pilling D, Curnow S, Falciani F . Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis. Arthritis Res Ther. 2006; 8(4):R120. PMC: 1779404. DOI: 10.1186/ar2009. View

10.

Lubberts E . The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015; 11(7):415-29. DOI: 10.1038/nrrheum.2015.53. View

11.

Kageyama Y, Kobayashi H, Kato N . Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis. Mod Rheumatol. 2009; 19(6):657-62. DOI: 10.1007/s10165-009-0217-6. View

12.

Rein P, Mueller R . Treatment with Biologicals in Rheumatoid Arthritis: An Overview. Rheumatol Ther. 2017; 4(2):247-261. PMC: 5696285. DOI: 10.1007/s40744-017-0073-3. View

13.

Yamada H, Nakashima Y, Okazaki K, Mawatari T, Fukushi J, Kaibara N . Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2007; 67(9):1299-304. DOI: 10.1136/ard.2007.080341. View

14.

Combe B . Progression in early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2009; 23(1):59-69. DOI: 10.1016/j.berh.2008.11.006. View

15.

Lubberts E, Schwarzenberger P, Huang W, Schurr J, Peschon J, van den Berg W . Requirement of IL-17 receptor signaling in radiation-resistant cells in the joint for full progression of destructive synovitis. J Immunol. 2005; 175(5):3360-8. DOI: 10.4049/jimmunol.175.5.3360. View

16.

Penatti A, Facciotti F, De Matteis R, Larghi P, Paroni M, Murgo A . Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2017; 19(1):103. PMC: 5437517. DOI: 10.1186/s13075-017-1305-1. View

17.

Guo Y, Wang N, Zhao S, Hou L, Xu Y, Zhang N . Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis. Chin Med J (Engl). 2013; 126(5):850-4. View

18.

Dalila A, Mohd Said M, Shaharir S, Asrul A, Low S, Shamsul A . Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis. Kaohsiung J Med Sci. 2014; 30(7):337-42. DOI: 10.1016/j.kjms.2014.02.010. View

19.

Vazquez-Tello A, Halwani R, Hamid Q, Al-Muhsen S . Glucocorticoid receptor-beta up-regulation and steroid resistance induction by IL-17 and IL-23 cytokine stimulation in peripheral mononuclear cells. J Clin Immunol. 2012; 33(2):466-78. DOI: 10.1007/s10875-012-9828-3. View

20.

Kondo N, Kuroda T, Kobayashi D . Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis. Int J Mol Sci. 2021; 22(20). PMC: 8539723. DOI: 10.3390/ijms222010922. View