Volume 3, Issue 5, October 2015, Page: 53-58
Interleukin-6: A Proinflammatory Role in Nephritis in Patients with Systemic Lupus Erythematosus
Dalia Abdul-Halim Shaheen, Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Cairo, Egypt
Hisham M. Habib, Department of Rheumatology and Rehabilitation, Faculty of Medicine, Mansoura University, Cairo, Egypt
Mohamed A. Marie, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Received: Aug. 12, 2015;       Accepted: Aug. 28, 2015;       Published: Sep. 17, 2015
DOI: 10.11648/j.ijgg.20150305.13      View  4959      Downloads  201
Abstract
Background. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a common finding of renal involvement which is related to high incidence of mortality and morbidity. IL-6 is produced by leukocytes and intrinsic kidney cells that affects inflammation, increases mesangial cell proliferation, and also contributes to autoimmunity. Objective. To detect the serum level as well as expression in PBMCs in the blood of IL-6 in SLE patients. Furthermore we compare serum level, as well as expression in PBMCs in the blood of IL-6 of lupus nephritis group versus non-nephritis lupus group and to study its correlation with other variables in SLE patients. Methods. The study was carried on 100 SLE patients, and 50 healthy control subjects. Fifty patients had lupus nephritis and 50 without evidence of lupus nephritis. Serum interleukin 6 (IL6) was measured using the ELISA technique as well as the expression of IL6 mRNA in PBMCs. Serum creatinine, C3, C4 and 24 hours urinary proteins were measured. Lupus activity was assessed using BILAG scoring system. Renal activity was measured using renal activity scoring system. Results. Serum IL6 level and its mRNA expression was significantly high in SLE patients and was higher in lupus nephritis patients than lupus patients without nephritis. IL6 was significantly correlated with renal activity score, 24 hours urinary proteins lowered C3 and C4 level and BILAG score. Conclusion. Serum IL-6 level and its mRNA expression is elevated in SLE patients as well as lupus nephritis patients. This was found to be linked with SLE disease activity in general and renal involvement in particular.
Keywords
Autoimmune, Cytokines, IL 6, SLE
To cite this article
Dalia Abdul-Halim Shaheen, Hisham M. Habib, Mohamed A. Marie, Interleukin-6: A Proinflammatory Role in Nephritis in Patients with Systemic Lupus Erythematosus, International Journal of Genetics and Genomics. Vol. 3, No. 5, 2015, pp. 53-58. doi: 10.11648/j.ijgg.20150305.13
Reference
[1]
Duarte C., Couto M., Ines L., Liang M. H. Epidemiology of systemic lupus erythematosus. In: Lahita R. G., Tsokos G., Buyon J., Koike T., editors. Systemic Lupus Erythematosus. 5th. London, UK: Elsevier; 2011. pp. 673–696.
[2]
Kistler AD. Lupusnephritis. Ther Umsch. 2015; 72(3):171-177.
[3]
Muñoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol. 2010; 15: 280–289. doi: 10.1038/nrrheum.2010.46.
[4]
Shao WH, Cohen PL. Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res Ther. 2011; 15: 202. doi: 10.1186/ar3535.
[5]
Alberto de Zubiria Salgado, Catalina Herrera-Diaz. Lupus Nephritis: An Overview of Recent Findings. Autoimmune Dis. 2012; 2012: 849684. Published online 2012 March 22. doi: 10.1155/2012/849684.
[6]
Tackey E, Lipsky PE, Illei GG. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus.2004; 13 (5):339–343.
[7]
Sanz AB, Sanchez-Nino MD, Ortiz A. TWEAK, a multifunctional cytokine in kidney injury. Kidney Int.2011; 80 (7):708–718.
[8]
Kitani A, Hara M, Hirose T, et al. Heterogeneity of B cell responsiveness to interleukin 4, interleukin 6 and low molecular weight B cell growth factor in discrete stages of B cell activation in patients with systemic lupus erythematosus. Clin Exp Immunol. 1989; 77 (1):31–36.
[9]
Kitani A, Hara M, Hirose T, et al. Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression. Clin Exp Immunol.1992; 88 (1):75–83.
[10]
Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood.1994; 83 (1):113–118.
[11]
Dai C, Wang H, Sung SS, Sharma R, Kannapell C, Han W, Wang Q, Davidson A, Gaskin F, Fu SM. Interferon alpha on NZM2328.Lc1R27: enhancing autoimmunity and immune complex-mediated glomerulonephritis without end stage renal failure. Clin Immunol. 2014 Sep; 154 (1):66-71. doi: 10.1016/j.clim.2014.06.008. Epub 2014 Jun 27.
[12]
McCarthy EM, Smith S, Lee RZ, Cunnane G, Doran MF, Donnelly S, Howard D, O'Connell P, Kearns G, Ní Gabhann J, Jefferies CA. The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients. Rheumatology (Oxford). 2014 Sep; 53(9):1586-1594. doi: 10.1093/rheumatology/ket428. Epub 2014 Apr 4.
[13]
Yougbaré I, Keravis T, Abusnina A, Decossas M, Schall N, Muller S, Lugnier C. Cyclic GMP catabolism up-regulation in MRL/lpr lupus-prone mice is associated with organ remodeling. Biochim Biophys Acta. 2014 Jul; 1842 (7):916-926. doi: 10.1016/j.bbadis.2014.03.001. Epub 2014 Mar 12.
[14]
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-1277.
[15]
Hay EM, Bacon PA, Gordon C Isenberg DA, Maddison P, Snaith ML, et al. The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. QJ Med 1993; 86: 447-458.
[16]
Schuett H, Luchtefeld M, Grothusen C, et al. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost 2009; 102: 215–222.
[17]
Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, et al. Systemic lupus international collaborating clinics renal activity/response exercise: Development of a renal activity score and renal response index. Arthritis & Rheumatism 2008; 58 (6), 1784–1788
[18]
Sabry A, Sheashaa H, El-Husseini A, Mahmoud K, Eldahshan KF, George SK, Abdel-Khalek E, El-Shafey EM, Abo-Zenah H. Cytokine. Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its correlation with disease activity. 2006 Aug; 35 (3-4):148-153. Epub 2006 Oct 5.
[19]
Zhu LJ1, Yang X, Yu XQ. Anti-TNF-alpha therapies in systemic lupus erythematosus. J Biomed Biotechnol. 2010; 2010: 465898. doi: 10.1155/2010/465898.
[20]
Kasitanon N, Magder LS, Petri M. Predictors of survival in systemic lupus erythematosus. Medicine (Baltimore). 2006; 85:147.
[21]
Lazennec G, Richmond A: Chemokines and chemokine receptors: New insights into cancer-related inflammation. Trends Mol Med. 2010; 16: 133–144.
[22]
Segerer S, Nelson PJ, Schlondorff D: Chemokines, chemokine receptors, and renal disease: From basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol. 2000; 11: 152–176.
[23]
Dienz O, Rincon M. The effects of IL-6 on CD4 T cell responses. Clin Immunol. 2009; 130: 27–33.
[24]
Li Y, Tucci M, Narain S, et al. Urinary biomarkers in lupus nephritis. Autoimmun Rev. 2006; 5: 383–388.
[25]
Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. 1988; 141: 1543–1549.
[26]
Tanigawa T, Nicola N, McArthur GA, Strasser A, Begley CG. Differential regulation of macrophage differentiation in response to leukemia inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression of the SCL transcription factor. Blood. 1995; 85: 379–390.
[27]
Richards HB, Satoh M, Shaw M, Libert C, Poli V, Reeves WH. Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. J Exp Med.1998; 188: 985–990.
[28]
Tackey E, Lipsky PE, Illei GG. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus.2004; 13 (5):339–343.
[29]
Rovin BH1, Parikh SV2. Lupus nephritis: the evolving role of novel therapeutics. Am J Kidney Dis. 2014 Apr; 63 (4):677-90. doi: 10.1053/j.ajkd.2013.11.023. Epub 2014 Jan 7.
[30]
Crow MK. Interferon pathway activation in systemic lupus erythematosus. Curr Rheumatol Rep. 2005; 7: 463–468.
[31]
Wei ZF, Jiao XL, Wang T, Lu Q, Xia YF, Wang ZT, et al. Norisoboldine alleviates joint destruction in rats with adjuvant-induced arthritis by reducing RANKL, IL-6, PGE2, and MMP-13 expression. Acta Pharmacol Sin. 2013; 34: 403–413.
[32]
Grondal G, Gunnarsson I, Ronnelid J, Rogberg S, Klareskog L, Lundberg I: Cytokine production, serum levels and disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 2000, 18:565-570.
[33]
Hagiwara E, Gourley MF, Lee S, Klinman DK: Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10: interferon-gamma-secreting cells in the peripheral blood. Arthritis Rheum 1996, 39:379-385.
[34]
Esposito P, Balletta MM, Procino A, Postiglione L, Memoli B: Interleukin-6 release from peripheral mononuclear cells is associated to disease activity and treatment response in patients with lupus nephritis. Lupus 2009, 18: 1329-1330.
[35]
Liang B, Gardner DB, Griswold DE, Bugelski PJ, Song XYR. Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus. Immunology.2006; 119: 296–305.
[36]
Ball EM, Gibson DS, Bell AL, Rooney MR. Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus. Lupus. 2014; 23(1):46-56.
[37]
Iwano M, Dohi K, Hirata E, et al. Urinary levels of IL-6 in patients with active lupus nephritis. Clinical Nephrology. 1993; 40 (1):16–21.
[38]
Herrera-Esparza R, Barbosa-Cisneros O, Villalobos-Hurtado R, Avalos-Díaz E. Renal expression of IL-6 and TNFα genes in lupus nephritis. Lupus. 1998; 7 (3):154–158.
[39]
Yung S1, Tsang RC, Sun Y, Leung JK, Chan TM. Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis. Journal of the American Society of Nephrology. 2005; 16 (11):3281–3294.
[40]
Peterson E, Robertson AD, Emlen W. Serum and urinary interleukin-6 in systemic lupus erythematosus.Lupus. 1996; 5 (6):571–575.
[41]
Ryffel B, Car BD, Gunn H, Roman D, Hiestand P, Mihatsch MJ. Interleukin-6 exacerbates glomerulonephritis in (NZB × NZW) F1 mice. Am J Pathol. 1994; 144 (5):927–937.
[42]
Yung S, Cheung KF, Zhang Q, Chan TM. Anti-dsDNA antibodies bind to mesangial annexin II in lupus nephritis. Journal of the American Society of Nephrology. 2010; 21(11):1912–1927.
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