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01-06-2018 | Original Article

Influence of corticosteroid therapy on IL-18 and nitric oxide production during Behçet’s disease

Authors: Fatmazohra Djaballah-Ider, Zineb Djeraba, Mourad Chemli, Nadjiba Dammene-Debbihe, Doulkifly Lounis, Houda Belguendouz, Yanis Medour, Samia Chaib, Chafia Touil-Boukoffa

Published in: Inflammopharmacology | Issue 3/2018

Abstract

Background and aims

Behçet’s disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients.

Methods

For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess’ method in naïve-active and corticosteroid-treated BD patients with different clinical manifestations. Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in these groups of patients.

Results and discussion

Our results indicate that IL-18 and nitrite levels were higher in naïve-active BD patients. Interestingly, this high production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and vascular involvement. Concerning corticosteroid treated-active BD patients, no difference was observed in this production between each clinical subgroup. However, IFN-γ levels increased in all categories of active patients. Interestingly, corticosteroid therapy reduced significantly these inflammatory mediators regardless of the clinical manifestations studied. In addition, the CD40/CD40L expression differed according to the clinical presentations.

Conclusion

Collectively, our results suggest that concomitant high production of IL-18 and NO in naïve-active BD patients is related to an increased risk of mucocutaneous lesions and vascular involvement. Moreover, the relationship between these two inflammatory markers could constitute a predictable tool of BD clinical presentations and an early factor of therapy efficiency.

Acikgoz N (2016) The neutrophil-lymphocyte ratio and Behcet disease. Angiology 67:297. https://doi.org/10.1177/0003319715611805 CrossRefPubMed

Akkurt ZM, Bozkurt M, Uçmak D, Yüksel H, Uçak H, Sula B, Gürsel Özkurt Z, Yildiz M, Akdeniz D, Arica M (2015) Serum cytokine levels in Behçet’s disease. J Clin Lab Anal 29:317–320. https://doi.org/10.1002/jcla.21772 CrossRefPubMed

Aktas Cetin E, Cosan F, Cefle A, Deniz G (2014) IL-22-secreting Th22 and IFN-γ-secreting Th17 cells in Behçet’s disease. Mod Rheumatol 24:802–807. https://doi.org/10.3109/14397595.2013.879414 CrossRefPubMed

Arroul-Lammali A, Djeraba Z, Belkhelfa M, Belguendouz H, Hartani D, Lahlou-Boukoffa OS, Touil-Boukoffa C (2012) Early involvement of nitric oxide in mechanisms of pathogenesis of experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein (IRBP). J Fr Ophtalmol 35:251–259. https://doi.org/10.1016/j.jfo.2011.05.003 CrossRefPubMed

Belguendouz H, Messaoudene D, Hartani D, Chachoua L, Ahmedi ML, Lahmar-Belguendouz K, Lahlou-Boukoffa O, Touil-Boukoffa C (2008) Effect of corticotherapy on interleukin-8 and -12 and nitric oxide production during Behçet and idiopathic uveitis. J Fr Ophtalmol 31:387–395CrossRefPubMed

Belguendouz H, Messaoudène D, Lahmar K, Ahmedi L, Medjeber O, Hartani D, Lahlou-Boukoffa O, Touil-Boukoffa C (2011) Interferon-γ and nitric oxide production during Behçet uveitis: immunomodulatory effect of interleukin-10. J Interferon Cytokine Res 31:643–651. https://doi.org/10.1089/jir.2010.0148 CrossRefPubMed

Belguendouz H, Messaoudene D, Lahmar-Belguendouz K, Djeraba Z, Otmani F, Terahi M, Tiar M, Hartani D, Lahlou-Boukoffa OS, Touil-Boukoffa C (2015) In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy. J Fr Ophtalmol 38:206–212. https://doi.org/10.1016/j.jfo.(2014).10.005 CrossRefPubMed

Ben Ahmed M, Houman H, Miled M, Dellagi K, Louzir H (2004) Involvement of chemokines and Th1 cytokines in the pathogenesis of mucocutaneous lesions of Behçet’s disease. Arthritis Rheum 50:2291–2295. https://doi.org/10.1002/art.20334 CrossRefPubMed

Chen F, Hou S, Jiang Z, Chen Y, Kijlstra A, Rosenbaum JT, Yang P (2012) CD40 gene polymorphisms confer risk of Behcet’s disease but not of Vogt-Koyanagi-Harada syndrome in a Han Chinese population. Rheumatol Oxf Engl 51:47–51. https://doi.org/10.1093/rheumatology/ker345 CrossRef

Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease (1990) Lancet. Lond Engl 335:1078–1080

Davatchi F, Shahram F, Chams-Davatchi C, Shams H, Nadji A, Akhlaghi M, Faezi T, Ghodsi Z, Faridar A, Ashofteh F, Sadeghi Abdollahi B (2010) Behcet’s disease: from East to West. Clin Rheumatol 29:823–833. https://doi.org/10.1007/s10067-010-1430-6 CrossRefPubMed

Davatchi F, Chams-Davatchi C, Shams H, Shahram F, Nadji A, Akhlaghi M, Faezi T, Ghodsi Z, Sadeghi Abdollahi B, Ashofteh F, Mohtasham N, Kavosi H, Masoumi M (2017) Behcet’s disease: epidemiology, clinical manifestations, and diagnosis. Expert Rev Clin Immunol 13:57–65. https://doi.org/10.1080/1744666X.2016.1205486 CrossRefPubMed

Di Mauro D, Bitto L, D’Andrea L, Favaloro A, Giacobbe O, Magaudda L, Rizzo G, Trimarchi F (2006) Behaviour of nitric oxide synthase isoforms in inflammatory human joint diseases: an immunohistochemical study. Ital J Anat Embryol 111:111–123PubMed

Direskeneli H (2006) Autoimmunity vs autoinflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatol Oxf Engl 45:1461–1465. https://doi.org/10.1093/rheumatology/kel329 CrossRef

Djaballah-Ider F, Chaib S, Belguendouz H, Talbi D, Touil-Boukoffa C (2012) T cells activation and interferon-γ/nitric oxide production during Behçet disease: a study in Algerian patients. Ocul Immunol Inflamm 20:215–217. https://doi.org/10.3109/09273948.2012.671882 CrossRefPubMed

Djeraba Z, Arroul-Lammali A, Medjeber O, Belguendouz H, Hartani D, Lahlou-Boukoffa O-S, Touil-Boukoffa C (2010) Nitric oxide, biomarker of experimental autoimmune uveitis induced by S antigen. J Fr Ophtalmol 33:693–700. https://doi.org/10.1016/j.jfo.2010.09.023 CrossRefPubMed

Djeraba Z, Boumedine K, Arroul-Lammali A et al (2014) Ex vivo immunomodulatory effect of all- trans-retinoic acid during Behçet’s disease: a study in Algerian patients. Immunopharmacol Immunotoxicol 36(1):78–86. https://doi.org/10.3109/08923973.2013.873048 CrossRefPubMed

Esatoglu SN, Kutlubay Z, Ucar D, Hatemi I, Uygunoglu U, Siva A, Hatemi G (2017) Behçet’s syndrome: providing integrated care. J Multidiscip Healthc 10:309–319. https://doi.org/10.2147/JMDH.S93681 CrossRefPubMedPubMedCentral

Evereklioglu C, Turkoz Y, Er H, Inaloz HS, Ozbek E, Cekmen M (2002) Increased nitric oxide production in patients with Behçet’s disease: is it a new activity marker? J Am Acad Dermatol 46:50–54CrossRefPubMed

Gracie JA, Robertson SE, McInnes IB (2003) Interleukin-18. J Leukoc Biol 73:213–224CrossRefPubMed

Hamzaoui K (2011) Th17 cells in Behçet’s disease: a new immunoregulatory axis. Clin Exp Rheumatol 29:S71–S76PubMed

Hamzaoui K, Hamzaoui A, Guemira F et al (2002) Cytokine profile in Behçet’s disease patients. Relationship with disease activity. Scand J Rheumatol 31(4):205–210CrossRefPubMed

Hamzaoui A, Ghraïri H, Ammar J, Zekri S, Guemira F, Hamzaoui K (2003) IL-18 mRNA expression and IFN-gamma induction in bronchoalveolar lavage from Behçet’s disease. Clin Exp Rheumatol 21:S8–14PubMed

Hamzaoui A, Houman MH, Massouadia M, Ben Salem T, Khanfir MS, Ben Ghorbel I, Miled M (2012) Contribution of Hla-B51 in the susceptibility and specific clinical features of Behcet’s disease in Tunisian patients. Eur J Intern Med 23:347–349. https://doi.org/10.1016/j.ejim.2011.12.011 CrossRefPubMed

Horie Y, Meguro A, Ohta T, Lee EB, Namba K, Mizuuchi K, Iwata D, Mizuki N, Ota M, Inoko H, Ishida S, Ohno S, Kitaichi N (2017) HLA-B51 carriers are susceptible to ocular symptoms of behçet disease and the association between the two becomes stronger towards the East along the silk road: a literature survey. Ocul Immunol Inflamm 25:37–40. https://doi.org/10.3109/09273948.2015.1136422 CrossRefPubMed

İnal EE, Rüstemoğlu A, İnanır A, Ekinci D, Gül Ü, Yiğit S, Ateş Ö (2015) Associations of rs4810485 and rs1883832 polymorphisms of CD40 gene with susceptibility and clinical findings of Behçet’s disease. Rheumatol Int 35:837–843. https://doi.org/10.1007/s00296-014-3171-3 CrossRefPubMed

İşcan Y, Yiğit U, Tuğcu BÇ, Erdoğan M, Erdoğan DA, Öner V, Taş M, Özyazgan Y (2012) Tear nitric oxide levels in Behçet’s disease. Med Kaunas Lith 48:559–562

Kapsimali VD, Kanakis MA, Vaiopoulos GA et al (2010) Etiopathogenesis of Behçet’s disease with emphasis on the role of immunological aberrations. Clin Rheumatol 29(11):1211–1216. https://doi.org/10.1007/s10067-010-1491-6 CrossRefPubMed

Li B, Yang P, Zhou H, Zhang Z, Xie C, Lin X, Huang X, Kijlstra A (2003) T-bet expression is up regulated in active Behçet’s disease. Br J Ophthalmol 87:1264–1267CrossRefPubMedPubMedCentral

Lopalco G, Lucherini OM, Vitale A, Talarico R, Lopalco A, Galeazzi M, Lapadula G, Cantarini L, Iannone F (2015) Putative role of serum amyloid-A and proinflammatory cytokines as biomarkers for Behcet’s disease. Medicine (Baltimore) 94:e1858. https://doi.org/10.1097/MD.0000000000001858 CrossRef

Lopalco G, Lucherini OM, Lopalco A, Venerito V, Fabiani C, Frediani B, Galeazzi M, Lapadula G, Cantarini L, Iannone F (2017) Cytokine signatures in mucocutaneous and ocular Behçet’s disease. Front Immunol. https://doi.org/10.3389/fimmu.2017.00200 CrossRefPubMedPubMedCentral

Musabak U, Pay S, Erdem H, Simsek I, Pekel A, Dinc A, Sengul A (2006) Serum interleukin-18 levels in patients with Behçet’s disease. Is its expression associated with disease activity or clinical presentations? Rheumatol Int 26:545–550. https://doi.org/10.1007/s00296-005-0029-8 CrossRefPubMed

Nair JR, Moots RJ (2017) Behcet’s disease. Clin Med Lond Engl 17:71–77. https://doi.org/10.7861/clinmedicine.17-1-71 CrossRef

Nakanishi K, Yoshimoto T, Tsutsui H et al (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474. https://doi.org/10.1146/annurev.immunol.19.1.423 CrossRefPubMed

Nara K, Kurokawa MS, Chiba S, Yoshikawa H, Tsukikawa S, Matsuda T, Suzuki N (2008) Involvement of innate immunity in the pathogenesis of intestinal Behçet’s disease. Clin Exp Immunol 152:245–251. https://doi.org/10.1111/j.1365-2249.2008.03626.x CrossRefPubMedPubMedCentral

Neves FS, Spiller F (2013) Possible mechanisms of neutrophil activation in Behçet’s disease. Int Immunopharmacol 17:1206–1210. https://doi.org/10.1016/j.intimp.2013.07.017 CrossRefPubMed

Neves FS, Carrasco S, Goldenstein-Schainberg C, Gonçalves CR, de Mello SBV (2009) Neutrophil hyperchemotaxis in Behçet’s disease: a possible role for monocytes orchestrating bacterial-induced innate immune responses. Clin Rheumatol 28:1403–1410. https://doi.org/10.1007/s10067-009-1261-5 CrossRefPubMed

Niles JC, Wishnok JS, Tannenbaum SR (2006) Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. Nitric Oxide Biol Chem 14:109–121. https://doi.org/10.1016/j.niox.2005.11.001 CrossRef

Palestine AG, Kolfenbach JR, Ozzello DJ (2016) Rheumatologists and ophthalmologists differ in treatment decisions for ocular Behçet disease. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis 22:316–319. https://doi.org/10.1097/RHU.0000000000000424 CrossRef

Rico D, Vaquerizas JM, Dopazo H et al (2007) Identification of conserved domains in the promoter regions of nitric oxide synthase 2: implications for the species-specific transcription and evolutionary differences. BMC Genomics 8:271. https://doi.org/10.1186/1471-2164-8-271 CrossRefPubMedPubMedCentral

Sancak B, Onder M, Oztas MO, Bukan N, Gürer MA (2003) Nitric oxide levels in Behçet’s disease. J Eur Acad Dermatol Venereol JEADV 17:7–9CrossRefPubMed

Schoenberger SP, Toes RE, van der Voort EI et al (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393(6684):480–483. https://doi.org/10.1038/31002 CrossRefPubMed

Shimizu J, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Yoshikawa H, Kaneko F, Suzuki T, Suzuki N (2012) Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet’s disease. Clin Exp Immunol 168:68–74. https://doi.org/10.1111/j.1365-2249.2011.04543.x CrossRefPubMedPubMedCentral

Takeuchi M, Karasawa Y, Harimoto K, Tanaka A, Shibata M, Sato T, Caspi RR, Ito M (2017) Analysis of Th Cell-related cytokine production in Behçet disease patients with uveitis before and after infliximab treatment. Ocul Immunol Inflamm 25:52–61. https://doi.org/10.3109/09273948.2016.1158276 CrossRefPubMed

Tanaka H, Yang G-X, Iwakoshi N, Knechtle SJ, Kawata K, Tsuneyama K, Leung P, Coppel RL, Ansari AA, Joh T, Bowlus C, Gershwin ME (2013) Anti-CD40 ligand monoclonal antibody delays the progression of murine autoimmune cholangitis. Clin Exp Immunol 174:364–371. https://doi.org/10.1111/cei.12193 CrossRefPubMedPubMedCentral

Taysi S, Sari RA, Dursun H, Yilmaz A, Keles M, Cayir K, Akyuz M, Uyanik A, Guvenc A (2008) Evaluation of nitric oxide synthase activity, nitric oxide, and homocysteine levels in patients with active Behcet’s disease. Clin Rheumatol 27:1529–1534. https://doi.org/10.1007/s10067-008-0963-4 CrossRefPubMed

Touil-Boukoffa C, Bauvois B, Sancéau J, Hamrioui B, Wietzerbin J (1998) Production of nitric oxide (NO) in human hydatidosis: relationship between nitrite production and interferon-gamma levels. Biochimie 80:739–744CrossRefPubMed

Tridetti J, Benoit A, Borgoens P et al (2016) Cardiovascular involvements in Behçet’s disease: “ANGIO-BEHÇET”. Rev Med Liege 71(1):22–27PubMed

Trottier MD, Newsted MM, King LE, Fraker PJ (2008) Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function. Proc Natl Acad Sci USA 105:2028–2033. https://doi.org/10.1073/pnas.0712003105 CrossRefPubMedPubMedCentral

Wang H, Yang P-Z, Peng X-Y, Zhao M, Zhou H-Y, Huang X-K (2017) An increased expression of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Behçet’s disease. Int J Ophthalmol 2:12–15

Xue L, Zhu X-H, Yang X-F, Bao X-C, Gao X-Q, Qiu Y-H, Wu Z, Ji X-P, Li H-W (2015) Effect of pioglitazone combined with simvastatin on the CD40-CD40 ligand system in rabbits with atherosclerosis. Eur Rev Med Pharmacol Sci 19:322–327PubMed

Yamamura M, Kawashima M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Morita Y, Ohmoto Y, Makino H (2001) Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis. Arthritis Rheum 44:275–285. https://doi.org/10.1002/1529-0131(200102)44:2<275::AID-ANR44>3.0.CO;2-B

Zeidan MJ, Saadoun D, Garrido M, Klatzmann D, Six A, Cacoub P (2016) Behçet’s disease physiopathology: a contemporary review. Auto-Immun Highlights 7:4. https://doi.org/10.1007/s13317-016-0074-1 CrossRefPubMedPubMedCentral

Zhang S-H, Zhang F-X (2017) Behcet’s disease with recurrent thoracic aortic aneurysm combined with femoral artery aneurysm: a case report and literature review. J Cardiothorac Surg. https://doi.org/10.1186/s13019-017-0644-y CrossRefPubMedPubMedCentral

Zhou ZY, Chen SL, Shen N et al (2012) Cytokines and Behcet’s disease. Autoimmun Rev 11(10):699–704. https://doi.org/10.1016/j.autrev.2011.12.005 CrossRefPubMed

Ziesche E, Bachmann M, Kleinert H, Pfeilschifter J, Mühl H (2007) The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells. J Biol Chem 282:16006–16015. https://doi.org/10.1074/jbc.M611040200 CrossRefPubMed

Title: Influence of corticosteroid therapy on IL-18 and nitric oxide production during Behçet’s disease
Authors: Fatmazohra Djaballah-Ider
Zineb Djeraba
Mourad Chemli
Nadjiba Dammene-Debbihe
Doulkifly Lounis
Houda Belguendouz
Yanis Medour
Samia Chaib
Chafia Touil-Boukoffa
Publication date: 01-06-2018
Publisher: Springer International Publishing
Published in: Inflammopharmacology / Issue 3/2018
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-018-0472-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Influence of corticosteroid therapy on IL-18 and nitric oxide production during Behçet’s disease

Abstract

Background and aims

Methods

Results and discussion

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background and aims

Methods

Results and discussion

Conclusion

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