Correlation between Serum IL-6 Level and Th17/Treg Ratio with Systemic Lupus Erythematosus Disease Activity
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Introduction: SLE pathophysiology shifted to a new paradigm which emphasizing the imbalance between Th17 and Treg. IL-6 is the main cytokine believed as the regulator of the balance between Th17 and Treg which play a big part in SLE pathophysiology and disease activity. The aim of this study was to determining the correlation between serum IL-6 level and Th17/Treg ratio with SLE disease activity on SLE inpatients of RSUD Dr. Soetomo Surabaya.
Methods: This cross sectional study included newly diagnosed SLE patients based on American College of Rheumatology (ACR) 1997 revised criteria and confirmed by rheumatologist. All subjects underwent the same examination and assessment such as SLE disease activity was scored according to SLAM score, serum IL-6 level measured using ELISA, and Th17/Treg ratio where the expression Th17-Treg detected by flowcytometry method.
Results: Thirty female subjects with active SLE had mean age 31,3 ± 10,46 years. The most frequent clinical manifestations were hematologic disorders and arthritis. Serum IL-6 level was significantly elevated in SLE patients compare to healthy subjects (200,61 pg/ml versus 45,9 pg/ml, p =0,028). Th17/Treg ratio were also significantly higher in SLE patients compared to healthy subjects (2,49 versus 1,20, p = 0,31). Th17/Treg ratio significantly correlated with SLE disease activity (r = 0,988; p<0,05). There were no significant correlation between serum IL-6 level with Th17/Treg ratio (r = -0,095; p>0,05) or even SLE disease activity (r = 0,066 ; p>0,05).
Conclusion: Serum IL-6 level had no significant correlation with Th17/Treg ratio or SLE disease activity. We found significant correlation between Th17/Treg ratio with SLE disease activity.
Abdel Galil SM, Ezzeldin N, El-Boshy ME. The role of serum IL-17 and IL-6 as biomarkers of disease activity and predictors of remission in patients with lupus nephritis. Cytokine [Internet]. 2015 Dec;76(2):280–7. Available from: http://dx.doi.org/10.1016/j.cyto.2015.05.007
Kasjmir YI, Handono K, Wijaya LK, Hamijoyo L, Albar Z, Kalim H, et al. Rekomendasi Perhimpunan Reumatologi Indonesia untuk Diagnosis dan Pengelolaan Lupus Eritematosus Sistemik [Internet]. 2011. 1-54 p. Available from: https://www.pbpapdi.org/images/file_guidelines/14_Rekomendasi_Lupus.pdf
Yao Y, Wang JB, Xin MM, Li H, Liu B, Wang LL, et al. Balance between inflammatory and regulatory cytokines in systemic lupus erythematosus. Genet Mol Res. 2016;15(2):1–8.
Mak, A Kow N. The Pathology of T Cells in Systemic Lupus Erythematosus. J Immunol Res. 2014;2014:1–9.
Moulton VR, Tsokos GC. Abnormalities of T cell signaling in systemic lupus erythematosus. 2011;13(2):207.
Fasching P, Stradner M, Graninger W, Dejaco C, Fessler J. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules. 2017;22(1).
Wang D, Huang S, Yuan X, Liang J, Xu R, Yao G, et al. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. Cell Mol Immunol. 2017;14(5):423–31.
Kimura A, Kishimoto T. IL-6: Regulator of Treg/Th17 balance. Eur J Immunol. 2010;40(7):1830–5.
Neurath MF, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev [Internet]. 2011;22(2):83–9. Available from: http://dx.doi.org/10.1016/j.cytogfr.2011.02.003
Paramaiswari A, Kertia N, Achadiyono DW. Relationship Between Systemic Lupus Activity Measurement (SLAM) Score and Mortality in Systemic Lupus Erytemathosus (SLE) Inpatients. J Intern Med Acta Interna. 2014;4(1):15–22.
Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007;27(5):461–6.
Umare V, Pradhan V, Nadkar M, Rajadhyaksha A, Patwardhan M, Ghosh KK, et al. Effect of proinflammatory cytokines (IL-6, TNF-alpha, and IL-1beta) on clinical manifestations in Indian SLE patients. Mediat Inflamm. 2014;2014:385297.
Ahmed N, Shigidi M, Al Agib AN, Abdelrahman H, Taha E. Clinical features and antinuclear antibodies profile among adults with systemic lupus erythematosus and lupus nephritis: a cross-sectional study. Pan Afr Med J. 2017;27:114.
Sabry A, Elbasyouni SR, Sheashaa HA, Alhusseini AA, Mahmoud K, George SK, et al. Correlation between levels of TNF-alpha; and IL-6 and hematological involvement in SLE Egyptian Patients with lupus nephritis. Int Urol Nephrol. 2006;38(3–4):731–7.
Tsokos GC. Systemic lupus erythematosus. N Engl J Med [Internet]. 2011;365:2110–21. Available from: https://www.nejm.org/doi/full/10.1056/NEJMra1100359
Treadwell EL, Wiley K, Word B, Melchior W, Tolleson WH, Gopee N, et al. Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at −1149G/T. J Immunol Res [Internet]. 2015;2015:1–10. Available from: http://dx.doi.org/10.1155/2015/435658
Handono K, Marisa D, Kalim H, Mawarti H. The associations among serum levels of vitamin D, TGF-β/IL-6 balance and Treg/Th17 balance in systemic lupus erythematosus patients in Indonesia. Int J Biochem Biotechnol [Internet]. 2013;2(9):490–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23585405
Galil SMA, Ezzeldin N, Said D, El-Boshy M. IL-17 is a key cytokine correlating with disease activity and clinical presentation of systemic lupus erythematosus. Indian J Rheumatol [Internet]. 2015 Dec;10(4):196–201. Available from: http://dx.doi.org/10.1016/j.injr.2015.06.003
Hammadi SS, Hussain M. Elevated Levels of IL- 6 in serum of SLE patients correlated with High- sensitivity CRP and ESR. Basrah J Sci. 2014;32(2):112–36.
Gröndal G, Gunnarsson I, Rönnelid J, Rogberg S, Klareskog L, Lundberg I. Cytokine production , serum levels and disease activity in systemic lupus erythematosus. Clin Exp Rheumatol [Internet]. 2000;18:565–70. Available from: https://www.clinexprheumatol.org/article.asp?a=1671
Peterson E, Robertson A, Emlen W. Urinary Interleukin-6 in Systemic Lupus Erythematosus. Lupus. 1996;5:571–5.
Dima A, Jurcut C, Balanescu P, Balanescu E, Badea C, Caraiola S, et al. Clinical significance of serum and urinary interleukin-6 in systemic lupus erythematosus patients. Egypt Rheumatol [Internet]. 2017;39(1):1–6. Available from: http://dx.doi.org/10.1016/j.ejr.2016.05.005
Ripley BJM, Goncalves B, Isenberg DA, Latchman DS, Rahman A. Raised levels of interleukin 6 in systemic lupus erythematosus correlate with anaemia. Ann Rheum Dis. 2005;64(6):849–53.
Eilertsen G, Nikolaisen C, Becker-Merok A, Nossent J. Interleukin-6 promotes arthritis and joint deformation in patients with systemic lupus erythematosus. Lupus [Internet]. 2011 May 21;20(6):607–13. Available from: http://journals.sagepub.com/doi/10.1177/0961203310392432
Yap DYH, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus - From bench to bedside. Nephrology. 2013;18(4):243–55.
Linker-israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-chen T, Klinenberg JR. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. J Immunol. 1991;147(1):117–23.
Klashman DJ, Martin RA, Martinez-maza O, Stevens RH. In vitro regulation of B cell differentiation by interleukin-6 and soluble CD23 in systemic lupus erythematosus B cell subpopulations and antigen-induced normal B cells. Arthritis Rheum. 1991;34(3):276–86.
Ma J, Yu J, Tao X, Cai L, Wang J, Zheng SG. The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients. Clin Rheumatol. 2010;29(11):1251–8.
Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X, et al. Th17 and natural treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60(5):1472–83.
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