Determination of Expression Levels of Interleukin 1, 6, 17, 23 and Tumor Necrosis Factor Genes in Patients with Systemic Lupus Erythematosus

Abstract

Purpose: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that can affect different organs of the body, especially the skin, joints, blood, kidneys and central nervous system. In our study, it was aimed to reveal the autoinflammatory events in the etiology of the disease by examining the expression levels of interleukin 1-6 tumor necrosis factor interleukin 17 interleukin 23 genes, which are thought to be involved in the inflammatory pathway. Material/ Method: It consists of 30 patients diagnosed with SLE and followed in Erzurum Atatürk University Health Research and Application Center Directorate, Physical Medicine and Rehabilitation Department Polyclinic. mRNA expression changes of IL-1, IL-6, IL-17, IL-23 and TNF-α genes were determined by quantitative Real Time PCR Results: Statistically significant differences were observed between the patient and control groups in IL-1, IL-17, IL-23 and TNF-α genes. Conclusion: No significant difference was found between the SLE and control groups in the study. The 3-fold significant difference of the IL-1 gene between the SLE group and the control group supports the important role of the IL-1 gene in the pathogenesis of SLE.

Keywords

• Pathogenesis
• Systemic Lupus Erythematosus
• Cytokines

References

1. Al-Maini MH, El-Ageb EM, Al-Wahaibi SS, et al. Demographic, autoimmune, and clinical profiles of patients with systemic lupus erythematosus in Oman. Rheumatol Int. 2003; 23: 186–191. Anisur Rahman, Ph. D and David A. Isenberg M.D. N Engl J Med 2008;358:929-39.
2. Dr.Onur Keskin. Sistemik Lupus Eritematozus hastalarında klinik bulgularla serum Iıl-17 ve IL-23 düzeylerinin incelenmesi. Ankara Üni. İç hastalıkları A.B.2010
3. Dong G, Ye R, Shi W, Liu S, Wang T, Yang X, Yang N, Yu X. IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Chinese Medical Journal [01 Apr 2003, 543-548
4. E.Svenungsson, G-Z Fei, K Jensen-Urstad, U de Faire, A Hamsten, J Frostegård. TNF-α: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease.Lupus, 2003.454-461
5. Edberg JC,Wu J, Langefeld CD, Brown EE, Marion MC, McGwin G Jr, Petri M, RamseyGoldman R, Reveille JD, Frank SG, Kaufman KM, Harley JB, Alarcón GS, Kimberly RP.
6. Genetic variation in the CRP promoter: association with systemic lupus erythematosus. Hum Mol Genet, 2008 Apr 15;17(8):1147-55.
7. Eilertsen GO, Beker-Merok A and Nossent JC, The influence of the 1997 updated classification criteria for systemic lupus erythematosus: epidemiology, disease presentation, and patient management. J Rheumatol. 2009; 36: 552–559.
8. ohnson SR, Urowitz MB, Ibañez D, et al. Ethnic variation in disease patterns and health outcomes in systemic lupus erythematosus. J Rheumatol. 2006; 33(10): 1990–1995.

9. Kusworini Handono, Dian Hasanah, Handono Kalim, Herin Mawarti.The associations among serum levels of vitamin D, TGF-β/IL-6 balance and Treg/Th17 balance in systemic lupus erythematosus patients in Indonesia.International Journal of Biochemistry and Biotechnology,2 April 2013.490-496
10. Laustrup H, Voss A, Gren A, et al. SLE disease patterns in a Danish population-based lupus cohort: An 8-year prospective study. Lupus. 2010; 19: 239–246.
11. Mak A & Kow NY. The Pathology of T Cells in Systemic Lupus Erythematosus. Journal of Immunology Research 2014; Article ID 419029, 8 pages.
12. 1Nath SK1, Han S, Kim-Howard X, Kelly JA, Viswanathan P, Gilkeson GS, Chen W, Zhu C, McEver RP, Kimberly RP, Alarcón-Riquelme ME, Vyse TJ, Li QZ, Wakeland EK, Merrill JT, James JA, Kaufman KM, Guthridge JM, Harley JB. A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet, 2008 Feb;40(2):152-4.
13. Naleway AL, Davis ME, Greenlee RT, et al. Epidemiology of systemic lupus erythematosus in rural Wisconsin. Lupus. 2005.862-866
14. Rees F, Doherty M, Grainge MJ, Lanyon P, Zhang W. The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies. Rheumatology 2017; 56(11):1945–1961.
15. Renner K et al. IL-3 contributes to development of lupus nephritis in MRL/lpr mice. Kidney Int. 2015; 88(5):1088-1098.
16. Xinfang Huang,Jing Hua,Nan Shen,Shunle Chen.Dysregulated expression of interleukin23 and interleukin-12 subunits in systemic lupus erythematosus patients. Taylor & Francis 06 Feb 2007.Pages 220-223
17. Vilar MJ and Sato EL, Estimating the incidence of systemic lupus erythematosus in a tropical region (Natal, Brazil). Lupus. 2002; 11: 528–532.
18. Rachel M et al. Analysis of Serum Interleukin (IL)-1β and IL-18 in Systemic Lupus Erythematosus. Front. Immunol. 2018; 9:1250.
19. Hye-Young Chun, Jae-Wook Chung, Hyoun-Ah Kim, Jeong-Moon Yun, Ja-Young Jeon, Young-Min Ye, Seung-Hyun Kim, Hae-Sim Park, Chang-Hee Su.Cytokine IL-6 and IL-10 as Biomarkers in Systemic Lupus Erythematosus. J Clin Immunol (2007) 27:461–466
20. Birner P, Heider S, Petzelbauer P, Wolf P, Kornauth C, Kuroll M, Merkel O, Steiner G, Kishimoto T, Rose-John S, Soleiman A, Moriggl R, Kenner L. Interleukin-6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus. Antibodies. 2016 Feb 13
21. Kusworini Handono, Dian Hasanah, Handono Kalim, Herin Mawarti.The associations among serum levels of vitamin D, TGF-β/IL-6 balance and Treg/Th17 balance in systemic lupus erythematosus patients in Indonesia.
22. Chun KwokWonga, Lydia Choi WanLita, Lai ShanTam,Edmund Kwok MingLi,Purple Tsz YanWong,Christopher Wai KeiLama.Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: Implications for Th17-mediated inflammation in autoimmunity.Elsevier June 2008, Pages 385-393
23. E.Svenungsson, G-Z Fei, K Jensen-Urstad, U de Faire, A Hamsten, J Frostegård. TNFα: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease.Lupus, 2003.454-461
24. A Sabry, A El-Husseini, Amr El-husseini, Khaleed Mahmoud, Khaleed F. Eldahshan, Shahir K. George, Ehab Abdel-Khalek, E.M. El-Shafey, Hamdy Abo-Zenah. Proinflammatory cytokines (TNF-a and IL- 6) in Egyptian patients with SLE: Its correlation with disease activity. Elsevier,2006.148-153
25. Süleyman Serdar Koca, Ilgın Karaca, Mustafa Ferzeyn Yavuzkır, Necati Dağlı, Metin Özgen, Bilal Üstündağ, Ahmet Işık.Insulin resistance is related with oxidative stress in systemic lupus erythematosus.AKD,2009.8-23