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European Cytokine Network

, Volume 29, Issue 3, pp 95–102 | Cite as

Increased IL-1β levels are associated with an imbalance of “oxidant/antioxidant” status during Behçet’s disease

  • Arezki Chekaoui
  • Karima Lahmar
  • Houda Belguendouz
  • Fettoum Mazari
  • Malika Terahi
  • Djenette Hakem
  • Pierre Youinou
  • Chafia Touil-BoukoffaEmail author
Original Article
  • 3 Downloads

Abstract

Background

Behçet’s disease is a multisystem disease. It stands at the crossroad between the autoimmunity and auto-inflammatory disorders. In this study, we sought to address a relationship that might exist between interleukin-1β (IL-1β) and the oxidants/antioxidants markers in Behçet’s patients.

Methods

Behçet’s disease patients (n = 78: active stage, n = 28; inactive stage, n = 50) and 41 healthy controls have been included in our study. In this context, we investigated the plasma levels of IL-1β and the nitrosative/oxidative markers: nitric oxide (NO), advanced oxidative protein products (AOPP) and fatty acids peroxidation-malondialdehyde (MDA). The antioxidant system was assessed by measuring the plasma level of superoxide dismutase (SOD) activity. The Mann-Whitney’s U and Pearson’s correlation tests were used for statistical analyses.

Results

Our case-control study showed that patients in active stage displayed higher plasma levels of IL-1β, NO, AOPP and MDA versus healthy controls and patients in inactive stage. Patients in active stage showed significantly lower SOD levels related to patients in inactive stage and healthy controls respectively, whereas patients in inactive stage showed statistically insignificant SOD level versus healthy controls. Correlation studies showed a significant positive correlation between IL-1β and AOPP, IL-1β and NO, and negative correlation between IL-1β and SOD among Behçet’s disease patients. In addition, we showed positive correlation between AOPP and NO, AOPP and MDA and negative correlation between NO and SOD, AOPP and SOD in Behçet’s disease patients.

Conclusion

Interestingly, our study revealed that IL-1β levels increased and correlated with an imbalance of oxidants/antioxidants system, especially during active stage of Behçet disease. Collectively, our study indicates a possible link between IL-1β production and nitrosative/oxidative markers during Behçet’s disease. Exploiting this relationship might provide valuable outputs in the follow-up and prognosis of Behçet’s disease with a potential therapeutic value.

Key words

Behçet’s disease IL-1β oxidative/nitrosative markers activation loop 

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References

  1. 1.
    Bhisitkul RB, Foster CS. Diagnosis and ophthalmological features of Behçet’s disease. Int Ophthalmol Clin 1996; 36: 127–34.CrossRefGoogle Scholar
  2. 2.
    Gurler A, Tursen U. Clinical manifestations of Behçet’s disease: an analysis of 2147 patients. Yonsei Med J 1997; 38: 423–7.CrossRefGoogle Scholar
  3. 3.
    Saadoun D, Wechsler B. Behcet’s disease. Orphanet J Rare Dis 2012; 7(1): p20.CrossRefGoogle Scholar
  4. 4.
    Evereklioglu C, Hamdi E, Turkoz Y, Cekmen M. Serum levels of TNF-α, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediators Inflamm 2002; 11(2): 87–93.CrossRefGoogle Scholar
  5. 5.
    Yosipovitch G, Shohat B, Bshara J, Wysenbeek A, Weinberger A. Elevated serum interleukin 1 receptors and interleukin 1B in patients with Behçet’s disease: correlations with disease activity and severity. Isr J Med Sci 1995; 31(6): 345–8.Google Scholar
  6. 6.
    Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 2005; 17(5): 586–99.CrossRefGoogle Scholar
  7. 7.
    Gül A. Behçet’s disease as an autoinflammatory disorder. Curr Drug Targets Inflamm Allergy 2005; 4(1): 81–3.CrossRefGoogle Scholar
  8. 8.
    Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev 2011; 22(4): 189–95.CrossRefGoogle Scholar
  9. 9.
    Simon A, van der Meer JW. Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes. Am J Physiol Regul Integr Comp Physiol 2007; 292(1): R86–98.CrossRefGoogle Scholar
  10. 10.
    Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009; 27: 621–68.CrossRefGoogle Scholar
  11. 11.
    Eksioglu-Demiralp E, Direskeneli H, Kibaroglu A, Yavuz S, Ergun T, Akoglu T. Neutrophil activation in Behcet’s disease. Clin Exp Rheumatol 2001; 19(24): 19–24.Google Scholar
  12. 12.
    Yazici C, Köse K, Caliş M, et al. Increased advanced oxidation protein products in Behçet’s disease: a new activity marker? Br J Dermatol 2004; 151(1): 105–11.CrossRefGoogle Scholar
  13. 13.
    Isik B, Aytekin S, Balci G. Serum levels of malonyldialdehyde (MDA) and paraoxonase activities in patients with Behcet’s disease. Clin Biochem 2009; 42(4):345.CrossRefGoogle Scholar
  14. 14.
    Tüzün A, Aydin A, Turan M. Erythrocyte antioxidant activity and trace element levels in Behçet’s disease. Biol Trace Elem Res 1998; 64(1-3): 169–74.CrossRefGoogle Scholar
  15. 15.
    Touil-Boukoffa C, Bauvois J, Sancèau B, Hamrioui B, Wietzerbin J. Production of nitric oxide (NO) in human hydatidosis: relationship between nitrite production and interferon-levels. Biochimie 1998; 80(8-9): 739–44.CrossRefGoogle Scholar
  16. 16.
    Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996; 9(5): 1304–13.CrossRefGoogle Scholar
  17. 17.
    Gül A. Pathogenesis of Behçet’s disease: autoinflammatory features and beyond. Semin Immunopathol 2015; 37(4):41.CrossRefGoogle Scholar
  18. 18.
    Ishigatsubo Y, Samukawa S. Behçet’s disease from the aspect of autoinflammatory disease. Jpn J Clin Immunol 2011; 34(5): 408–19.CrossRefGoogle Scholar
  19. 19.
    Ben-Chetrit E, Cohen R, Chajek-Shaul T. Familial mediterranean fever and Behçet’s disease-are they associated? J Rheumatol 2002; 29: 530–4.Google Scholar
  20. 20.
    Aksu K, Keser G. Coexistence of vasculitidies with familial Mediterranean fever. Rheumatol Int 2011; 31(10): 1263–74.CrossRefGoogle Scholar
  21. 21.
    Mege JL, Dilsen N, Sanguedolce V, et al. Overproduction of monocyte derived tumor necrosis factor alpha, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet’s disease. A comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol 1993; 20: 1544–9.Google Scholar
  22. 22.
    Hamzaoui K, Hamza M, Ayed K. Production of TNF-alpha and IL-1 in active Behçet’s disease. J Rheumatol 1990; 17(10): 1428–9.Google Scholar
  23. 23.
    Katayama T, Tachinami K, Ishiguro M, Kubota Y. The relation between Behçet’s disease and interleukin-1 beta production. Nippon Ganka Gakkai Zasshi 1994; 98(2): 197–201.Google Scholar
  24. 24.
    Barrett J, Ollier WER, Thornhill M, Gul A. Association of specific interleukin 1 gene cluster polymorphisms with increased susceptibility for Behçet’s disease. Rheumatology 2003; 42(7): 860–4.CrossRefGoogle Scholar
  25. 25.
    Shimizu J, Takai K, Takada E, et al. Possible association of proinflammatory cytokines including IL1βandTNFαwith enhanced Th17 cell differentiation in patients with Behçet’s disease. Clin Rheumatol 2016; 35(7): 1857–63.CrossRefGoogle Scholar
  26. 26.
    Gül A, Esin S, Dilsen N, et al. Immunohistology of skin pathergy reaction in Behçet’s disease. Br J Dermatol 1995; 132(6): 901–7.CrossRefGoogle Scholar
  27. 27.
    Nur Rifaioglu E, Bülbülşen B, Ekiz Ö, Cigdem Dogramaci A. Neutrophil to lymphocyte ratio in Behçet’s disease as a marker of disease activity. Acta Dermatovenerol Alp Panonica Adriat 2014; 23: 65–67..Google Scholar
  28. 28.
    Niwa Y, Miyake S, Sakane T, Shingu M, Yokoyama M. Autooxidative damage in Behçet’s disease-endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils. Clin Exp Immunol 1982; 49(1): 247–55.Google Scholar
  29. 29.
    Nauseef WM. Myeloperoxidase in human neutrophil host defence. Cell Microbiol 2014; 16(8): 1146–55.CrossRefGoogle Scholar
  30. 30.
    Yazici C, Köse K, Caliş M, et al. Increased advanced oxidation protein products in Behçet’s disease: a new activity marker? Br J Dermatol 2004; 151(1): 105–11.CrossRefGoogle Scholar
  31. 31.
    Esra Birben E, Murat Sahiner U, Sackesen C. Oxidative stress and antioxidant defense. World Allergy Organ J 2012; 5(1): 9–19.CrossRefGoogle Scholar
  32. 32.
    Sandikci R, Türkmen S, Güvenen G, et al. Lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet’s disease. Acta Dermatovenerol 2003; 83(5): 342–6.Google Scholar
  33. 33.
    Orem A, Efe H, Deger O, et al. Relationship between lipid peroxidation and disease activity in patients with Behçet’s disease. J Dermatol Sci 1997; 16(1): 11–6.CrossRefGoogle Scholar
  34. 34.
    Bozkurt M, Yüksel H, Em Y, et al. Serum prolidase enzyme activity and oxidative status in patients with Behçet’s disease. Redox Rep 2014; 19(2): 59–64.CrossRefGoogle Scholar
  35. 35.
    Belguendouz H, Messaoudene D, Lahmar K, et al. Interferon-γ and nitric oxide production during Behçet uveitis: immunomodulatory effect of interleukin-10. J Interferon Cytokine Res 2001; 31(6): 43–51.Google Scholar
  36. 36.
    Ahmedi ML, Belguendouz H, Messaoudene D, et al. Influence of steroid hormones on the production of two inflammatory markers, IL-12 and nitric oxide, in Behçet’s disease. J Fr Ophtalmol 2015; 39(4): 333–40.CrossRefGoogle Scholar
  37. 37.
    Akdeniz N, Esrefoglu M, Keleş MS, Karakuzu A, Atasoy M. Serum interleukin-2, interleukin-6, tumour necrosis factor-alpha and nitric oxide levels in patients with Behcet’s disease. Ann Acad Med Singapore 2004; 33(5): 596–9.Google Scholar
  38. 38.
    Belguendouz H, Lahmar-Belguendouz K, Messaoudene D, et al. Cytokines modulate the “immune-metabolism” interactions during Behçet disease: effect on arginine metabolism. Int J Inflamm 2015; 9: 241738.Google Scholar
  39. 39.
    Akcay YD, Sagin FG, Aksu K, et al. A panel of oxidative stress assays does not provide supplementary diagnostic information in Behçet’s disease patients. J Inflamm 2012; 9:13.CrossRefGoogle Scholar
  40. 40.
    Servettaz A, Guilpain P, Goulvestre C, et al. Radical oxygen species production induced by advanced oxidation protein products predicts clinical evolution and response to treatment in systemic sclerosis. Ann Rheum Dis 2007; 66(9): 1202–9.CrossRefGoogle Scholar
  41. 41.
    Buldanlioglu S, Turkmen S, Ayabakan HB, et al. Nitric oxide, lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet’s disease. Br J Dermatol 2005; 153(3): 526–30.CrossRefGoogle Scholar
  42. 42.
    Tüzün A, Aydın A, Turan M. Erythrocyte antioxidant activity and trace element levels in Behçet’s disease. Biol Trace Elem Res 1997; 64(1-3): 169–74.CrossRefGoogle Scholar
  43. 43.
    Aydin E, Sogut S, Ozyurt H, et al. Comparison of serum nitric oxide, malondialdehyde levels, and antioxidant enzyme activities in Behçet’s disease with and without ocular disease. Ophthalmic Res 2004; 36(3): 177–82.CrossRefGoogle Scholar
  44. 44.
    Kiraz S, Ertenli I, Calguneri M, et al. Interactions of nitric oxide and superoxide dismutase in Behçet’s disease. Clin Exp Rheumatol 2001; 19(24): S25–9.Google Scholar
  45. 45.
    Liang L, Tan X, Zhou Q, et al. IL-1β triggered by peptidoglycan and lipopolysaccharide through TLR2/4 and ROS-NLRP3 inflammasome-dependent pathways is involved in ocular Behçet’s disease. Invest Ophthalmol Vis Sci 2013; 54(1): 402–14.CrossRefGoogle Scholar
  46. 46.
    Liu SX, Hou FF, Guo ZJ, et al. Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation. Arterioscler Thromb Vasc Biol 2006; 26: 1156–62.CrossRefGoogle Scholar
  47. 47.
    Iwao Y, Nakajou K, Nagai R, et al. CD36 is one of important receptors promoting renal tubular injury by advanced oxidation protein products. Am J Physiol Renal Physiol 2008; 295: 1871–80.CrossRefGoogle Scholar
  48. 48.
    Meissner F, Molawi K, Zychlinsky A. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 2008; 9(8): 866–72.CrossRefGoogle Scholar
  49. 49.
    Dongli Y, Elner SG, Bian ZM, et al. Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells. Exp Eye Res 2007; 85(4): 462–72.CrossRefGoogle Scholar

Copyright information

© John Libbey Eurotext 2018

Authors and Affiliations

  • Arezki Chekaoui
    • 1
  • Karima Lahmar
    • 1
  • Houda Belguendouz
    • 1
  • Fettoum Mazari
    • 2
  • Malika Terahi
    • 2
  • Djenette Hakem
    • 3
  • Pierre Youinou
    • 4
  • Chafia Touil-Boukoffa
    • 1
    Email author
  1. 1.USTHB, “Cytokines and NO Synthases” team, LBCM, FSBBab ezzouar, AlgiersAlgeria
  2. 2.Ophtalmology DepartmentCHU Nafissa HammoudAlgiersAlgeria
  3. 3.Internal Medicine DepartmentCHU Med Lamine DebbaghineAlgiersAlgeria
  4. 4.Laboratory of Excellence (Labex) IGO, INSERM ERI29European University of BrittanyBrestFrance

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