Distinct Cytokine Patterns Associated With Rheumatoid Arthritis Disease Activity
Pola Sitokin yang Berbeda Terkait Dengan Aktivitas Penyakit Artritis Reumatoid
DOI:
https://doi.org/10.21070/ijhsm.v2i1.161Keywords:
Rheumatoid Arthritis, Cytokines, IL-6, TNF-α, BiomarkersAbstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation and joint destruction, driven in part by dysregulated cytokine activity. Specific Background: Pro-inflammatory and anti-inflammatory cytokines are central to RA pathogenesis, yet their potential as reliable predictors of disease activity remains underutilized in routine clinical practice. Knowledge Gap: Traditional RA activity markers lack specificity regarding immune pathways, and the diagnostic value of cytokine profiling, especially in relation to sex-based differences, remains unclear. Aim: This study aimed to evaluate serum levels of IL-6, TNF-α, IL-1β, IL-10, and IFN-γ in RA patients versus healthy controls, and assess their correlation with disease activity. Results: RA patients exhibited significantly elevated IL-6, TNF-α, IL-1β, and IFN-γ, and reduced IL-10 (p<0.001). Cytokine levels positively (or inversely for IL-10) correlated with disease activity, with ROC analysis confirming their diagnostic utility. Novelty: The study highlights gender-specific cytokine variations, notably higher IL-6 and lower IL-10 in females, providing insight into sex-based immunopathology. Implications: These findings support cytokine profiling as a promising tool for RA diagnosis and activity monitoring, and underscore the need for personalized, cytokine-targeted therapeutic strategies.
Highlight :
-
Cytokine markers predict RA activity – Elevated IL-6, TNF-α, IL-1β, and IFN-γ correlate with disease severity.
-
IL-10 is a key anti-inflammatory marker – Lower levels are linked to worse RA outcomes.
-
ROC analysis confirms diagnostic value – IL-6 had the highest diagnostic accuracy (AUC = 0.91).
Keywords : Rheumatoid Arthritis, Cytokines, IL-6, TNF-α, Biomarkers
References
[1] N. Kondo, T. Kuroda, and D. Kobayashi, "Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis," International Journal of Molecular Sciences, 2021.
[2] S. Alivernini, G. S. Firestein, and I. B. McInnes, "The Pathogenesis of Rheumatoid Arthritis," Immunity, 2022.
[3] Q. Ding, W. Hu, R. Wang, Q. Yang et al., "Signaling Pathways in Rheumatoid Arthritis: Implications for Targeted Therapy," Signal Transduction and Targeted Therapy, 2023.
[4] A. Markovics, K. S. Rosenthal, K. Mikecz, R. E. Carambula et al., "Restoring the Balance Between Pro-Inflammatory and Anti-Inflammatory Cytokines in the Treatment of Rheumatoid Arthritis: New Insights From Animal Models," Biomedicines, 2021.
[5] A. Tylutka, L. Walas, and A. Zembron-Lacny, "Level of IL-6, TNF, and IL-1beta and Age-Related Diseases: A Systematic Review and Meta-Analysis," Frontiers in Immunology, 2024.
[6] S. K. Dhar, K. Vishnupriyan, S. Damodar, S. Gujar et al., "IL-6 and IL-10 as Predictors of Disease Severity in COVID-19 Patients: Results From Meta-Analysis and Regression," Heliyon, 2021.
[7] A. A. Hamad, H. M. Mustafa, and O. A. Mohsein, "Detection of the Levels of Immune Cytokines (IL-4, IL-5, TNF-alpha) in School-Age and Preschoolers With an Ascaris Lumbricoides Infection," Journal of Parasitic Diseases, vol. 48, no. 4, pp. 782–787, 2024.
[8] M. Wei and C. Q. Chu, "Prediction of Treatment Response: Personalized Medicine in the Management of Rheumatoid Arthritis," Best Practice and Research: Clinical Rheumatology, 2022.
[9] M. Colina and G. Campana, "Precision Medicine in Rheumatology: The Role of Biomarkers in Diagnosis and Treatment Optimization," Journal of Clinical Medicine, 2025.
[10] J. M. Guthridge, C. A. Wagner, and J. A. James, "The Promise of Precision Medicine in Rheumatology," Nature Medicine, 2022.
[11] N. Deol, V. Nuno, M. Schuman, and C. Contreras, "An Osteopathic Approach to Complex Regional Pain Syndrome (CRPS)," AAO Journal, 2021.
[12] S. S. Taylor, N. Noor, I. Urits, A. Paladini et al., "Complex Regional Pain Syndrome: A Comprehensive Review," Pain and Therapy, 2021.
[13] L. Meert, "Unravelling the Role of and the Interrelation Between Somatosensory Function and Metabolic Factors in Chronic (Postsurgical) OA Pain," unpublished, 2024.
[14] N. A. Abdulmuttaleb, M. Q. Mohammed, and O. A. Mohsein, "Exploring the Connection Between Inflammatory Cytokines, Hypertension, and Diabetes in Angina Patients," Cytokines, vol. 14, no. 15, p. 16, 2024.
[15] L. Zhang, R. Zhang, and L. Li, "Effects of Probiotic Supplementation on Exercise and the Underlying Mechanisms," Foods, 2023.
[16] K. Onnheim, S. Huang, A. S. Holmertz et al., "Rheumatoid Arthritis Chondrocytes Produce Increased Levels of Pro-Inflammatory Proteins," Cartilage Open, 2022.
[17] S. Shufang and X. Xiaojiao, "Pro-Inflammatory Cytokine IL-21 Correlates With the Reactive Oxygen Species and 25-Hydroxy Vitamin D in Rheumatoid Arthritis Patients," Immunity, [n.d.].
[18] Z. K. Abbas et al., "Immunological Biomarkers and Their Role in the Diagnosis and Prognosis of Leishmaniasis: A Case–Control Study," Tropical Parasitology, vol. 15, no. 1, pp. 33–41, 2025.
[19] J. Xiao, R. Wang, W. Zhou, X. Cai et al., "LncRNA NEAT1 Regulates the Proliferation and Production of the Inflammatory Cytokines in Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting miR-204-5p," Human Cell, 2021.
[20] S. Nirenjen, J. Narayanan, T. Tamilanban et al., "Exploring the Contribution of Pro-Inflammatory Cytokines to Impaired Wound Healing in Diabetes," Frontiers in Immunology, 2023.
[21] Q. Lu, Z. Zhu, C. Tan, H. Zhou et al., "Changes of Serum IL-10, IL-1beta, IL-6, MCP-1, TNF-alpha, IP-10 and IL-4 in COVID-19 Patients," Journal of Clinical Laboratory Analysis, 2021.
[22] H. Islam, G. S. Jackson, J. S. Yoon et al., "Sex Differences in IL-10’s Anti-Inflammatory Function: Greater STAT3 Activation and Stronger Inhibition of TNF-alpha Production in Male Blood Leukocytes ex vivo," American Journal of Physiology: Cell Physiology, 2022.
[23] N. Subramanian, B. Tavira, K. Hofwimmer et al., "Sex-Specific Regulation of IL-10 Production in Human Adipose Tissue in Obesity," Frontiers in Immunology, 2022.
[24] K. Dissanayake, C. Jayasinghe, P. Wanigasekara et al., "Potential Applicability of Cytokines as Biomarkers of Disease Activity in Rheumatoid Arthritis: ELISPOT-Based Evaluation of TNF-alpha, IL," PLoS One, 2021.
[25] A. M. A. Faqri et al., "The Role of Cytokines in Autoimmune Diseases: Pathogenesis and Therapeutic Implications," Central Asian Journal of Medical and Natural Sciences, vol. 6, no. 3, pp. 852–873, 2025.
[26] H. Wang, R. Zhang, J. Shen, Y. Jin et al., "Circulating Level of Blood Iron and Copper Associated With Inflammation and Disease Activity of Rheumatoid Arthritis," Biological Trace Element Research, 2023.
[27] C. Liu, D. Chu, K. Kalantar-Zadeh, and J. George, "Cytokines: From Clinical Significance to Quantification," Advances in Clinical Chemistry, 2021.
[28] A. E. R. Kartikasari, C. S. Huertas, A. Mitchell et al., "Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis," Frontiers in Immunology, 2021.
[29] S. Shekhar, A. K. Yadav, A. Khosla, and P. R. Solanki, "Interleukins Profiling for Biosensing Applications: Possibilities and the Future of Disease Detection," ECS Sensors Plus, 2022.
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Zainab Abd Mohammed

This work is licensed under a Creative Commons Attribution 4.0 International License.