Higher Circulating Concentration of Interleukin-38 in Patients with Knee Osteoarthritis: Its Association with Disease Severity
Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel anti-inflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity.
Blood specimens were collected from two groups including 23newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA).
Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores >5 werehigher than those with WOMAC scores<40, and VASscores<5 (p=0.026 and p=0.035, respectively). The IL-38 levels in OA patients with body mass index (BMI)<25 were also significantly higher than in patients with BMI>25 (p=0.05).
According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner.The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.
2. Greene MA, Loeser RF. Aging-related inflammation in osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1966-71.
3. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther. 2017;19(1):18.
4. Lopes EBP, Filiberti A, Husain SA, Humphrey MB. Immune Contributions to Osteoarthritis. Curr Osteoporos Rep. 2017;15(6):593-600.
5. Xu WD, Huang AF. Role of Interleukin-38 in Chronic Inflammatory Diseases: A Comprehensive Review. Front Immunol. 2018;9:1462.
6. Zeinali M, Hadian Amree A, Khorramdelazad H, Karami H, Abedinzadeh M. Inflammatory and anti‐inflammatory cytokines in the seminal plasma of infertile men suffering from varicocele. Andrologia. 2017;49(6):e12685.
7. Xu W-D, Su L-C, He C-S, Huang A-F. Plasma interleukin-38 in patients with rheumatoid arthritis. Int Immunopharmacol. 2018;65:1-7.
8. Veerdonk FVD, Netea M. New insights in the immunobiology of IL-1 family members. Front هmmunol. 2013;4:167.
9. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29(8):1039-1049.
10. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15(12):1833-40.
11. Imamura M, Ezquerro F, Marcon Alfieri F, et al. Serum levels of proinflammatory cytokines in painful knee osteoarthritis and sensitization. Int J Inflam. 2015;2015:329792.
12. Jafarzadeh A, Nemati M, Rezayati MT. Serum levels of interleukin (IL)-27 in patients with ischemic heart disease. Cytokine. 2011;56(2):153-6.
13. Takenaka SI, Kaieda S, Kawayama T, et al. IL-38: A new factor in rheumatoid arthritis. Biochem Biophys Rep. 2015;4:386-91.
14. Boutet MA, Bart G, Penhoat M, et al. Distinct expression of interleukin (IL)-36alpha, beta and gamma, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease. Clin Exp Immunol. 2016;184(2):159-73.
15. Rudloff I, Godsell J, Nold-Petry CA, et al. Brief Report: Interleukin-38 Exerts Antiinflammatory Functions and Is Associated With Disease Activity in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2015;67(12):3219-25.
16. Takeuchi Y, Seki T, Kobayashi N, et al. Analysis of serum IL-38 in juvenile-onset systemic lupus erythematosus. Mod Rheumatol. 2018;28(6):1069-72.
17. Chu M, Tam LS, Zhu J, et al. In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice. Immunobiology. 2017;222(3):483-93.
18. Li J, Liu L, Rui W, et al. New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions. Dermatology. 2017;233(1):37-46.
19. Wang SL, Zhang R, Hu KZ, Li MQ, Li ZC. Interleukin-34 Synovial Fluid Was Associated with Knee Osteoarthritis Severity: A Cross-Sectional Study in Knee Osteoarthritis Patients in Different Radiographic Stages. Dis Markers. 2018;2018:2095480.
20. Li B, Zhang YL, Yu SY. Synovial Fluid Eotaxin-1 Levels May Reflect Disease Progression in Primary Knee Osteoarthritis Among Elderly Han Chinese: A Cross-Sectional Study. Cartilage. 2018:1947603518764280.
21. Das Gupta E, Ng WR, Wong SF, Bhurhanudeen AK, Yeap SS. Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population. PLoS One. 2017;12(9):e0184802.
22. Askari A, Naghizadeh MM, Homayounfar R, et al. Increased Serum Levels of IL-17A and IL-23 Are Associated with Decreased Vitamin D3 and Increased Pain in Osteoarthritis. PLoS One. 2016;11(11):e0164757.
23. Kuipers EN, van Dam AD, Ballak DB, et al. IL-37 Expression Reduces Lean Body Mass in Mice by Reducing Food Intake. Int J Mol Sci. Aug 2 2018;19(8).
|Issue||Vol 20 No 1 (2021)|
|Articular cartilage IL-38 protein Inflammation mediators Joint diseases Osteoarthritis|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|