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IL-1β, IL-18 and Caspase-1 Levels in Serum as an Early Marker in Familial Mediterranean Fever Patients with Attack and Attack-free Period

Yıl 2021, Cilt 11, Sayı 4, 494 - 499, 31.07.2021

Öz

Introduction: In the pathogenesis of the FMF disease, cytokines play important roles in the inflammation of the serous membranes. This study aims to investigate the relationship between serum levels of IL-1β, IL-18 and caspase-1 with CRP, ESR, fibrinogen and immune response attack/attack-free period. Material and Method: 60 patients diagnosed with FMF according to Tel-Hashomer criteria were divided into two groups as attack and attack-free period. Serum cytokine levels were examined by the ELISA method in 60 patients and 30 HCs, and the relationship between acute phase reactants and immune response was investigated. Results: A significant increase in serum concentrations of pro-inflammatory cytokines IL-1β (p = 0.001), IL-18 (p = 0.043) and caspase-1 (p = 0.043) was observed in FMF attack patients compared to control.. And also, IL-1β levels were positively correlated with neutrophils, ESR and CRP in FMF attack patients and there was a relationship between disease severity and IL-1β. In FMF attack-free patients, while a trend towards increased serum IL-1β (p=0.075) and IL-18 (p=0.516) levels were noted, it did not reach statistical significance. However, a significant difference was observed in the caspase-1 (p=0.049) levels of attack-free according to HCs. Conclusion: This study suggests that IL-1β, IL-18 and caspase-1 can serve as a useful marker not only in the attack period but also in the attack-free period, and provide a useful clue for the diagnosis and treatment of the disease.

Kaynakça

  • [1] K. Migita, T. Asano, S. Sato, T. Koga, Y. Fujita, ve A. Kawakami, “Familial Mediterranean fever: overview of pathogenesis, clinical features and management”, Immunol. Med., c. 41, sayı 2, ss. 55–61, 2018, doi: 10.1080/13497413.2018.1481579.
  • [2] H. Van Gorp vd., “Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation”, Proc. Natl. Acad. Sci. U. S. A., c. 113, sayı 50, ss. 14384–14389, Ara. 2016, doi: 10.1073/pnas.1613156113.
  • [3] E. Sohar, J. Gafni, M. Pras, ve H. Heller, “Familial Mediterranean fever”, Am. J. Med., c. 43, sayı 2, ss. 227–253, Ağu. 1967, doi: 10.1016/0002-9343(67)90167-2.
  • [4] C. Korkmaz, H. Özdogan, O. Kasapçopur, ve H. Yazici, “Acute phase response in familial Mediterranean fever”, Ann. Rheum. Dis., c. 61, sayı 1, ss. 79–81, 2002, doi: 10.1136/ard.61.1.79.
  • [5] C. A. Dinarello, “Overview of the IL-1 family in innate inflammation and acquired immunity”, Immunological Reviews, c. 281, sayı 1. Blackwell Publishing Ltd, ss. 8–27, 2018, doi: 10.1111/imr.12621.
  • [6] P. Skendros vd., “Translational and clinical immunology Regulated in development and DNA damage responses 1 (REDD1) links stress with IL-1b-mediated familial Mediterranean fever attack through autophagy-driven neutrophil extracellular traps”, 2017, doi: 10.1016/j.jaci.2017.02.021.
  • [7] P. R. Hesker, M. T. Nguyen, M. Kovarova, J. P. Y. Ting, ve B. H. Koller, “Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels”, PLoS One, c. 7, sayı 11, doi: 10.1371/journal.pone.0051105.
  • [8] S. Grandemange, I. Aksentijevich, I. Jeru, A. Gul, ve I. Touitou, “The regulation of MEFV expression and its role in health and familial Mediterranean fever”, Genes Immun., c. 12, sayı 7, ss. 497–503, Eki. 2011, doi: 10.1038/gene.2011.53.
  • [9] C. Lorente-Sorolla, M. G. Netea, ve E. Ballestar, “Epigenetics in Autoinflammation”, içinde Textbook of Autoinflammation, Springer International Publishing, 2019, ss. 49–60.
  • [10] K. Yildirim vd., “Relationship between serum interleukin-1β levels and acute phase response proteins in patients with familial Mediterranean fever”, Biochem. Medica, c. 22, sayı 1, ss. 109–113, 2012, doi: 10.11613/bm.2012.012.
  • [11] A. Akdeniz vd., “Ailevi Akdeniz Ateşi Genetik Özellikleri ve SistemikHastalıklarla İlişkisi”, 2020.
  • [12] K. Yildirim vd., “Relationship between serum interleukin – 1β levels and acute phase response”, Biochem. Medica, c. 22, sayı 1, ss. 109–113, 2012.
  • [13] J. J. Chae vd., “The Familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-{kappa}B through its N-terminal fragment”, Blood, c. 112, sayı 5, ss. 1794–1803, Eyl. 2008, doi: 10.1182/blood-2008-01-134932.
  • [14] D. Novick, S. Kim, G. Kaplanski, ve C. A. Dinarello, “Interleukin-18, more than a Th1 cytokine”, Seminars in Immunology, c. 25, sayı 6. Academic Press, ss. 439–448, Ara. 15, 2013, doi: 10.1016/j.smim.2013.10.014.
  • [15] D. Álvarez-Errico, R. Vento-Tormo, ve E. Ballestar, “Genetic and epigenetic determinants in autoinflammatory diseases”, Front. Immunol., c. 8, sayı MAR, Mar. 2017, doi: 10.3389/fimmu.2017.00318.
  • [16] S. Haznedaroglu vd., “Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever”, Clin. Exp. Rheumatol., c. 23, sayı 4 SUPPL 38, 2005.
  • [17] I. Simsek vd., “Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever”, Rheumatol. Int., c. 27, sayı 9, ss. 807–811, 2007, doi: 10.1007/s00296-006-0301-6.
  • [18] F. Gohar vd., “Correlation of Secretory Activity of Neutrophils With Genotype in Patients With Familial Mediterranean Fever”, Arthritis Rheumatol., c. 68, sayı 12, ss. 3010–3022, Ara. 2016, doi: 10.1002/art.39784.
  • [19] M. G. Netea, F. L. Van De Veerdonk, J. W. M. Van Der Meer, C. A. Dinarello, ve L. A. B. Joosten, “Inflammasome-independent regulation of IL-1-family cytokines”, Annu. Rev. Immunol., c. 33, ss. 49–77, Mar. 2015, doi: 10.1146/annurev-immunol-032414-112306.
  • [20] H. Ozdogan ve S. Ugurlu, “Familial Mediterranean Fever”, Press. Medicale, c. 48, sayı 1, ss. e61–e76, 2019, doi: 10.1016/j.lpm.2018.08.014.
  • [21] G. Manukyan, R. Aminov, G. Hakobyan, ve T. Davtyan, “Accelerated apoptosis of neutrophils in familial Mediterranean fever”, Front. Immunol., c. 6, sayı MAY, 2015, doi: 10.3389/fimmu.2015.00239.
  • [22] Y. Bozkurt, A. Demir, B. Erman, ve A. Gül, “Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes”, Comput. Math. Methods Med., c. 2015, 2015, doi: 10.1155/2015/893507.
  • [23] A. Livneh vd., “Criteria for the diagnosis of familial Mediterranean fever”, Arthritis Rheum., c. 40, sayı 10, ss. 1879–1885, 1997, doi: 10.1002/art.1780401023.
  • [24] E. Pras vd., “Clinical differences between North African and Iraqi Jews with familial Mediterranean fever”, Am. J. Med. Genet., c. 75, sayı 2, ss. 216–219, Oca. 1998, doi: 10.1002/(SICI)1096-8628(19980113)
  • [25] C. Notarnicola, M. N. Didelot, F. Seguret, J. Demaille, ve I. Touitou, “Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever”, Genes Immun., c. 3, sayı 1, ss. 43–45, 2002, doi: 10.1038/sj.gene.6363813.
  • [26] Z. B. Özçakar, S. Özdel, S. Yılmaz, E. D. Kurt-Şükür, M. Ekim, ve F. Yalçınkaya, “Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis”, Clin. Rheumatol., c. 35, sayı 2, ss. 441–446, 2016, doi: 10.1007/s10067-014-2772-2.
  • [27] A. Soriano, E. Verecchia, A. Afeltra, R. Landolfi, ve R. Manna, “IL-1β biological treatment of familial mediterranean fever”, Clinical Reviews in Allergy and Immunology, c. 45, sayı 1. ss. 117–130, Ağu. 2013, doi: 10.1007/s12016-013-8358-y.
  • [28] M. Hacımustafaoğlu vd., “Akut Faz Reaktanları (Eritrosit Sedimentasyon Hızı, CRP) Acute Phase Reactants (Erythrocyte Sedimentation Rate, CRP)”, J Pediatr Inf, c. 11, ss. 53–55, 2017, doi: 10.5578/ced.201701.
  • [29] T. Wada vd., “Longitudinal analysis of serum interleukin-18 in patients with familial Mediterranean fever carrying MEFV mutations in exon 10”, Cytokine, c. 104, sayı October, ss. 143–146, 2018, doi: 10.1016/j.cyto.2017.10.007.
  • [30] F. Moghaddas, R. Llamas, ve … D. D. N., “A novel Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to Familial Mediterranean”, ard.bmj.com, 2017,
  • [31] J. W. Yu vd., “Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization”, Cell Death Differ., c. 13, sayı 2, ss. 236–249, Şub. 2006, doi: 10.1038/sj.cdd.4401734.
  • [32] A. Omenetti, S. Carta, L. Delfino, A. Martini, M. Gattorno, ve A. Rubartelli, “Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: Correlation with MEFV genotype” doi: 10.1136/annrheumdis-2012-202774.
  • [33] J. J. Chae vd., “The B30.2 domain of pyrin, the familial mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production”, Proc. Natl. Acad. Sci. U. S. A., c. 103, sayı 26, ss. 9982–9987, doi: 10.1073/pnas.0602081103.
  • [34] E. Apostolidou vd., “Neutrophil extracellular traps regulate IL-1β-mediated inflammation in familial Mediterranean fever”, Ann. Rheum. Dis., c. 75, sayı 1, ss. 269–277, doi: 10.1136/annrheumdis-2014-205958.

Ailesel Akdeniz Ateşi Hastalarında Atak ve Remisyon Döneminde Erken Bir Belirteç Olarak Serum IL-1β, IL-18 ve Kaspaz-1 Düzeylerinin Değerlendirilmesi

Yıl 2021, Cilt 11, Sayı 4, 494 - 499, 31.07.2021

Öz

Giriş: FMF hastalığının patogenezinde sitokinler, seröz membranların iltihaplanmasında önemli rol oynarlar. Bu çalışmanın amacı, serum IL–1β, IL-18 ve kaspaz-1 serum düzeylerinin atak ve remisyon dönemde CRP, ESR, fibrinojen ve immün yanıt ile ilişkisini araştırmaktır. Gereç ve Yöntem: Tel-Hashomer kriterlerine göre FMF tanısı almış 60 hasta atak ve remisyon dönemi olarak iki gruba ayrıldı. 60 FMF hastasının ve 30 kontrol grubu bireyin serum sitokin düzeyleri ELISA yöntemi ile incelendi ve akut faz reaktanları ile immün yanıt arasındaki ilişki araştırıldı. Bulgular: Pro-inflamatuar sitokinler olan IL-1β (p = 0.001), IL-18 (p = 0.043) ve kaspaz-1 (p = 0.043) serum konsantrasyonlarında FMF atak dönemi hastalarında kontrole kıyasla belirgin bir artış gözlemlendi. Ayrıca, IL-1β seviyeleri, FMF atak hastalarında nötrofiller, ESR ve CRP ile pozitif korelasyon gösterdi ve hastalık şiddeti ile IL-1β arasında bir ilişki saptandı. Remisyon dönemi hastalarda ise. serum IL-1β (p = 0.075) ve IL-18 (p = 0.516) düzeylerinde artışa yönelik bir eğilim kaydedilirken, istatistiksel anlamlılığa ulaşmadı. Bununla birlikte, kaspaz-1 (p = 0,049) seviyesinde kontrole nazaran anlamlı bir artış gözlemlendi. Sonuç: Bu çalışma, IL-1β, IL-18 ve kaspaz-1’in sadece atak döneminde değil, ataklar arası dönemde de yararlı bir belirteç olarak hizmet edebileceğini ve hastalığın tanı ve tedavisi için yararlı bir ipucu sağladığını ileri sürmektedir.

Kaynakça

  • [1] K. Migita, T. Asano, S. Sato, T. Koga, Y. Fujita, ve A. Kawakami, “Familial Mediterranean fever: overview of pathogenesis, clinical features and management”, Immunol. Med., c. 41, sayı 2, ss. 55–61, 2018, doi: 10.1080/13497413.2018.1481579.
  • [2] H. Van Gorp vd., “Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation”, Proc. Natl. Acad. Sci. U. S. A., c. 113, sayı 50, ss. 14384–14389, Ara. 2016, doi: 10.1073/pnas.1613156113.
  • [3] E. Sohar, J. Gafni, M. Pras, ve H. Heller, “Familial Mediterranean fever”, Am. J. Med., c. 43, sayı 2, ss. 227–253, Ağu. 1967, doi: 10.1016/0002-9343(67)90167-2.
  • [4] C. Korkmaz, H. Özdogan, O. Kasapçopur, ve H. Yazici, “Acute phase response in familial Mediterranean fever”, Ann. Rheum. Dis., c. 61, sayı 1, ss. 79–81, 2002, doi: 10.1136/ard.61.1.79.
  • [5] C. A. Dinarello, “Overview of the IL-1 family in innate inflammation and acquired immunity”, Immunological Reviews, c. 281, sayı 1. Blackwell Publishing Ltd, ss. 8–27, 2018, doi: 10.1111/imr.12621.
  • [6] P. Skendros vd., “Translational and clinical immunology Regulated in development and DNA damage responses 1 (REDD1) links stress with IL-1b-mediated familial Mediterranean fever attack through autophagy-driven neutrophil extracellular traps”, 2017, doi: 10.1016/j.jaci.2017.02.021.
  • [7] P. R. Hesker, M. T. Nguyen, M. Kovarova, J. P. Y. Ting, ve B. H. Koller, “Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels”, PLoS One, c. 7, sayı 11, doi: 10.1371/journal.pone.0051105.
  • [8] S. Grandemange, I. Aksentijevich, I. Jeru, A. Gul, ve I. Touitou, “The regulation of MEFV expression and its role in health and familial Mediterranean fever”, Genes Immun., c. 12, sayı 7, ss. 497–503, Eki. 2011, doi: 10.1038/gene.2011.53.
  • [9] C. Lorente-Sorolla, M. G. Netea, ve E. Ballestar, “Epigenetics in Autoinflammation”, içinde Textbook of Autoinflammation, Springer International Publishing, 2019, ss. 49–60.
  • [10] K. Yildirim vd., “Relationship between serum interleukin-1β levels and acute phase response proteins in patients with familial Mediterranean fever”, Biochem. Medica, c. 22, sayı 1, ss. 109–113, 2012, doi: 10.11613/bm.2012.012.
  • [11] A. Akdeniz vd., “Ailevi Akdeniz Ateşi Genetik Özellikleri ve SistemikHastalıklarla İlişkisi”, 2020.
  • [12] K. Yildirim vd., “Relationship between serum interleukin – 1β levels and acute phase response”, Biochem. Medica, c. 22, sayı 1, ss. 109–113, 2012.
  • [13] J. J. Chae vd., “The Familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-{kappa}B through its N-terminal fragment”, Blood, c. 112, sayı 5, ss. 1794–1803, Eyl. 2008, doi: 10.1182/blood-2008-01-134932.
  • [14] D. Novick, S. Kim, G. Kaplanski, ve C. A. Dinarello, “Interleukin-18, more than a Th1 cytokine”, Seminars in Immunology, c. 25, sayı 6. Academic Press, ss. 439–448, Ara. 15, 2013, doi: 10.1016/j.smim.2013.10.014.
  • [15] D. Álvarez-Errico, R. Vento-Tormo, ve E. Ballestar, “Genetic and epigenetic determinants in autoinflammatory diseases”, Front. Immunol., c. 8, sayı MAR, Mar. 2017, doi: 10.3389/fimmu.2017.00318.
  • [16] S. Haznedaroglu vd., “Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever”, Clin. Exp. Rheumatol., c. 23, sayı 4 SUPPL 38, 2005.
  • [17] I. Simsek vd., “Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever”, Rheumatol. Int., c. 27, sayı 9, ss. 807–811, 2007, doi: 10.1007/s00296-006-0301-6.
  • [18] F. Gohar vd., “Correlation of Secretory Activity of Neutrophils With Genotype in Patients With Familial Mediterranean Fever”, Arthritis Rheumatol., c. 68, sayı 12, ss. 3010–3022, Ara. 2016, doi: 10.1002/art.39784.
  • [19] M. G. Netea, F. L. Van De Veerdonk, J. W. M. Van Der Meer, C. A. Dinarello, ve L. A. B. Joosten, “Inflammasome-independent regulation of IL-1-family cytokines”, Annu. Rev. Immunol., c. 33, ss. 49–77, Mar. 2015, doi: 10.1146/annurev-immunol-032414-112306.
  • [20] H. Ozdogan ve S. Ugurlu, “Familial Mediterranean Fever”, Press. Medicale, c. 48, sayı 1, ss. e61–e76, 2019, doi: 10.1016/j.lpm.2018.08.014.
  • [21] G. Manukyan, R. Aminov, G. Hakobyan, ve T. Davtyan, “Accelerated apoptosis of neutrophils in familial Mediterranean fever”, Front. Immunol., c. 6, sayı MAY, 2015, doi: 10.3389/fimmu.2015.00239.
  • [22] Y. Bozkurt, A. Demir, B. Erman, ve A. Gül, “Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes”, Comput. Math. Methods Med., c. 2015, 2015, doi: 10.1155/2015/893507.
  • [23] A. Livneh vd., “Criteria for the diagnosis of familial Mediterranean fever”, Arthritis Rheum., c. 40, sayı 10, ss. 1879–1885, 1997, doi: 10.1002/art.1780401023.
  • [24] E. Pras vd., “Clinical differences between North African and Iraqi Jews with familial Mediterranean fever”, Am. J. Med. Genet., c. 75, sayı 2, ss. 216–219, Oca. 1998, doi: 10.1002/(SICI)1096-8628(19980113)
  • [25] C. Notarnicola, M. N. Didelot, F. Seguret, J. Demaille, ve I. Touitou, “Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever”, Genes Immun., c. 3, sayı 1, ss. 43–45, 2002, doi: 10.1038/sj.gene.6363813.
  • [26] Z. B. Özçakar, S. Özdel, S. Yılmaz, E. D. Kurt-Şükür, M. Ekim, ve F. Yalçınkaya, “Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis”, Clin. Rheumatol., c. 35, sayı 2, ss. 441–446, 2016, doi: 10.1007/s10067-014-2772-2.
  • [27] A. Soriano, E. Verecchia, A. Afeltra, R. Landolfi, ve R. Manna, “IL-1β biological treatment of familial mediterranean fever”, Clinical Reviews in Allergy and Immunology, c. 45, sayı 1. ss. 117–130, Ağu. 2013, doi: 10.1007/s12016-013-8358-y.
  • [28] M. Hacımustafaoğlu vd., “Akut Faz Reaktanları (Eritrosit Sedimentasyon Hızı, CRP) Acute Phase Reactants (Erythrocyte Sedimentation Rate, CRP)”, J Pediatr Inf, c. 11, ss. 53–55, 2017, doi: 10.5578/ced.201701.
  • [29] T. Wada vd., “Longitudinal analysis of serum interleukin-18 in patients with familial Mediterranean fever carrying MEFV mutations in exon 10”, Cytokine, c. 104, sayı October, ss. 143–146, 2018, doi: 10.1016/j.cyto.2017.10.007.
  • [30] F. Moghaddas, R. Llamas, ve … D. D. N., “A novel Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to Familial Mediterranean”, ard.bmj.com, 2017,
  • [31] J. W. Yu vd., “Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization”, Cell Death Differ., c. 13, sayı 2, ss. 236–249, Şub. 2006, doi: 10.1038/sj.cdd.4401734.
  • [32] A. Omenetti, S. Carta, L. Delfino, A. Martini, M. Gattorno, ve A. Rubartelli, “Increased NLRP3-dependent interleukin 1β secretion in patients with familial Mediterranean fever: Correlation with MEFV genotype” doi: 10.1136/annrheumdis-2012-202774.
  • [33] J. J. Chae vd., “The B30.2 domain of pyrin, the familial mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production”, Proc. Natl. Acad. Sci. U. S. A., c. 103, sayı 26, ss. 9982–9987, doi: 10.1073/pnas.0602081103.
  • [34] E. Apostolidou vd., “Neutrophil extracellular traps regulate IL-1β-mediated inflammation in familial Mediterranean fever”, Ann. Rheum. Dis., c. 75, sayı 1, ss. 269–277, doi: 10.1136/annrheumdis-2014-205958.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Orjinal Araştırma
Yazarlar

Feyzanur YILDIRIMTEPE ÇALDIRAN
TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ
0000-0001-7778-194X
Türkiye


Şenol ÇİTLİ
RECEP TAYYİP ERDOĞAN ÜNİVERSİTESİ
0000-0001-6226-4712
Türkiye


Ercan ÇAÇAN
TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ
0000-0002-3487-9493
Türkiye


Köksal DEVECİ (Sorumlu Yazar)
GAZIOSMANPASA UNIVERSITY, FACULTY OF MEDICINE
0000-0003-1531-8567
Türkiye

Destekleyen Kurum Tokat Gaziosmanpasa University, Scientific Research Projects Commission.
Proje Numarası [BAP 2019/84
Teşekkür Not applicable.
Yayımlanma Tarihi 31 Temmuz 2021
Kabul Tarihi 29 Nisan 2021
Yayınlandığı Sayı Yıl 2021, Cilt 11, Sayı 4

Kaynak Göster

AMA Yıldırımtepe Çaldıran F. , Çitli Ş. , Çaçan E. , Deveci K. IL-1β, IL-18 and Caspase-1 Levels in Serum as an Early Marker in Familial Mediterranean Fever Patients with Attack and Attack-free Period. J Contemp Med. 2021; 11(4): 494-499.