Proinflammatory Cytokines (TNF alpha and IL-6) in Egyptian SLE Patients With Lupus Nephritis

Abstract

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Keywords

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Proinflammatory Cytokines (TNF alpha and IL-6) in Egyptian SLE Patients With Lupus Nephritis

Abstract

Aim: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by a wide variety of autoantibodies, some of which are pathogenic. In recent years it has become more evident that the polyclonal B cell activation in SLE is T-cell dependent. To investigate whether serum levels of TNF-α and IL-6 is higher in Egyptian patients with SLE- presented with lupus nephritis -than healthy control volunteers and its correlation with the clinical activity in patients with different activity scores as measured by Systemic Lupus Erythmatosus Disease Activity Index (SLEADI). Methods: Sixty individuals (40 patients with SLE and 20 healthy control volunteers) were the subject of this study, they were subjected to thorough clinical examination, laboratory investigations, their clinical disease activity was scored according to SLEDAI, and serum sampling was obtained for TNF-α and IL-6 levels assay. Renal biopsy was carried out for all patients. Results: The mean level of TNF-α was (766.95±357.82 ρg/ml) for patients with active disease while it was (314.01±100.87ρg/ml) for those with inactive disease -the difference was statistically significant (p=0.002), and (172.7±39.19ρg/ml) for the healthy control group. The mean level of IL-6 was (135.4±54.23ρg/ml) for patients with active disease while it was (47.33±18.61ρg/ml) for those with inactive disease - the difference was statistically significant (p=0.002), and (21.15±10.99ρg/ml) for the healthy control group. A significant correlations between TNF-α and IL-6 serum levels and the SLEDAI score was observed (r =0.743 and 0.772 respectively). Conclusion: Serum TNF-α and IL-6 are sensitive markers for SLE disease activity. They may be useful independent markers for prediction of SLE disease activity and to differentiate normal subjects from those having SLE. Their possible therapeutic implications in the treatment of SLE in the future deserve wide scale trials. Key words: SLE, lupus nephritis, TNF-α, IL6.

Keywords

• SLE, lupus nephritis, TNF-α, IL6

References

1. Brink I, Thiele B, Burmester GR, Trebeljahr G, Emmrich F, Hiepe F. Effects of anti-CD4 antibodies on the release of IL-6 and TNF-a in whole blood samples from patients with systemic lupus erythematosus. Lupus 1999;8:723-30
2. Lauwerys BR. Houssiau FA. Involvement of Cytokines in the Pathogenesis of Systemic Lupus Erythematosus. Adv Exp Med Biol 2003;520:237-51
3. Aringer M, Zimmermann C, Graninger WB et al. TNF-α is an essential mediator in lupus nephritis. Arthritis Rheum 2002; 46:3418-9
4. Gabay C, Cakir N, Moral F et al. Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol 1997;24:303-8
5. Studnicka-Benke A, Steiner G, Petera P, Smolen JS. Tumour necrosis factor- α and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol 1996;35:1067-74
6. Al-Janadi M, al-Balla S, Al-Dalaan A, Raziuddin S. Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases. J Clin Immunol 1993;13:58-67
7. Spronk PE, ter Borg EJ, Limburg PC, Kallenberg CG. Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity. Clin Exp Immunol 1992;90:106-110
8. Linker Israeli M. Cytokine abnormalities in Immunopathol 1972;63:10-12 Clin Immunol

9. Lacki JK, SamborskiW,Mackiewicz SH. Interleukin-10 and interleukin- 6 in lupus erythematosus and rheumatoid arthritis, correlations with acute phase proteins. Clin Rheumatol 1997;16:275-8
10. Tan EM, Cohen AS, Fries JI et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-7
11. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992;35:630-40
12. Aderka D, Engelman H, Maor Y, Brakebusch C, Wallach D. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992; 75(2):323-9
13. Montero-Julian FA,Gautherot E, Wijdenes J, Klein B, Brailly H. Pharmacokinetics of interlukin-6 during therapy with anti- interlukin-6 enhanced clearance of interlukin-6 by a combination of three anti-interlukin-6 antibodies. J Interferon Res 1994;14(5): 301-2 14- Pisetsky antibodies: DS. Anti-DNA and autoantibodies. Curr Opin Rheumatol 2000;12:364-8
14. Madaio MP. The role of autoantibodies in the pathogenesis of lupus nephritis. Semin Nephrol 1999;19:48–56
15. Jacobs C, Pawlak R, Mikeska E et al. Systemic lupus erythmatosus and rheumatoid arthritis differ from healthy controls in their cytokine pattern after stress exposure. Lupus 2001;40:868-75
16. Rieckmann P, Tuscano JM, Kehrl JH. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in B-lymphocyte function. Methods 1997;11:128-32
17. Strand V. Monoclonal antibodies and other biologic therapies. Lupus 2001;10: 216-21
18. Maury CP, Teppo AM. Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. Arthritis Rheum 1989;32:146-50
19. Mahmoud RA, El-Gendi HI, Ahmed HH. Serum neopterin, tumor necrosis factor- alpha and soluble tumor necrosis factor receptor II (p75) levels and disease activity in Egyptian female patients with systemic lupus erythematosus. Clin Biochem 2005;38(2):134-41
20. Munk ME, Anding P, Schettini AP, Cunha MG, Kaufmann SH. Soluble tumor necrosis factor alpha receptors in sera from leprosy patients. Infect Immun 1999;67(1):423-5
21. Kelly JA, Moser KL, Harley JB: The genetics of systemic lupus erythematosus: putting the pieces together. Genes Immun 2002;3(Suppl):S71-S85
22. Horwitz DA, Jacob CO. The cytokine network in the pathogenesis of systemic lupus therapeutic Immunopathol 1994;16:181-200 possible Semin implications.
23. Hiepe F, Volk HD, Apostolff E et al. Treatment of severe systemic lupus erythematosus with anti-CD4 monoclonal antibody. Lancet 1991;338: 1529-30
24. Malide D, Russo P, Bendayan M. Presence of tumor necrosis factor alpha and interleukin-6 in renal mesangial cells of lupus nephritis patients. Hum Pathol 1995;26:558-64
25. Finck BK, Chan B, Wofsy D. Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. J Clin Invest 1994;94:585-91
26. Hirohata S, Miyamoto, T. Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 1990;33: 644-9
27. Raskovic S, Bogic M, Peric-Popadic A et al. Laporatory and morphologic parameters in patients with lupus nephritis. Spr Arh Celock Lek. 2002:130 (3)38-41