Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin

ertek, belkıs; Deniz, Gunnur; Pur Ozyigit, Leyla; Aktaş, Esin; Kucuksezer, Umut Can; Gelincik, Aslı; Demir, Semra; Buyukozturk, Suna

doi:10.25002/tji.2020.1339

Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin

Belkıs ERTEK, (İstanbul Üniversitesi, Aziz Sancar Deneysel Tıp Enstitüsü (Aziz Sancar DETAE), İmmünoloji Anabilim Dalı, İstanbul, Türkiye)

Semra DEMİR, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Alerji Bilim Dalı, İstanbul, Türkiye)

Umut Can KÜÇÜKSEZER, (İstanbul Üniversitesi, Aziz Sancar Deneysel Tip Enstitüsü (Aziz Sancar DETAE), İmmünoloji Anabilim Dalı, İstanbul, Türkiye)

Leyla PUR ÖZYİĞİT, (University Hospitals of Leicester, Department of Allergy and Immunology, United Kingdom)

Aslı GELİNCİK, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Alerji Bilim Dalı, İstanbul, Türkiye)

Suna BÜYÜKÖZTÜRK, (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Alerji Bilim Dalı, İstanbul, Türkiye)

Gunnur DENIZ, (İstanbul Üniversitesi, Aziz Sancar Deneysel Tıp Enstitüsü (Aziz Sancar DETAE), İmmünoloji Anabilim Dalı, İstanbul, Türkiye)

ESİN ÇETİN (İstanbul Üniversitesi, Aziz Sancar Deneysel Tıp Enstitüsü (Aziz Sancar DETAE), İmmünoloji Anabilim Dalı, İstanbul, Türkiye)

Turkish Journal of Immunology

2 0

Yıl: 2020 Cilt: 8 Sayı: 3 Sayfa Aralığı: 120 - 128 Metin Dili: İngilizce DOI: 10.25002/tji.2020.1339 İndeks Tarihi: 28-12-2021

Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin

Öz:

Introduction: Ciprofloxacin (CPFX), a frequently prescribed quinolone, may induce cutaneous adverse drug reactions. Delayed type hypersensitivity reactions (DTHR) are often difficult to deal with, therefore, in vitro testing for DTHR is the long-anticipated method for their management. This study aimed to evaluate potential value of lymphocyte transformation test (LTT) and intracellular cytokine secretion of drug stimulated CD4+ T cells in patients with DTHR against ciprofloxacin. Material and Methods: Patients experienced DTHR with CPFX (n=8) and healthy subjects (n=10) were enrolled. CPFX skin prick, patch and intradermal tests were performed. LTT by flow cytometry aimed to determine CPFXspecific CD4+ T cell proliferation. Intracellular IL-4, IL-10, IL-2 & IFN-γ levels were analysed by flow cytometry in CPFX-specific CD4+T cells. Cytokine contents of cell culture supernatants were evaluated by ELISA. Results: In patients with DTHR, 5 and 10 μg/mL CPFX induced significant CD4+T cell proliferation (p=0.014 and p=0.05, respectively). IL-2 (p=0.02, p=0.001 and p=0.001, respectively) and IL-4 (p=0.001) secreting CD4+T cell percentages were increased, while IFN-γ+(p=0.001, p=0.011 and p=0.012, respectively) and IL-10+(p=0.001, p=0.001 and p=0.002, respectively) CD4+T cells were decreased. The cell culture supernatants revealed downregulated IL-10 (p<0.000, p=0.004, p=0.001 and p=0.0001, respectively) and upregulated IL-4 levels (p=0.003, p=0.013 and p=0.0001, respectively) in patients, regardless of CPFX stimulation. Intradermal test was positive in only one patient while all patch tests remained negative. Conclusion: Our findings suggest that the increase of IL-2 and IL-4-secreting CD4+T cells together with the decrease of IL-10 and IFN-γ-secreting CD4+ T cells is related to DTHR seen in patients with delayed-type CPFX allergy. Intracellular cytokine measurement, together with LTT could ease the management of CPFX hypersensitivity when in vivo tests are non-available, remain inconclusive or negative.

Anahtar Kelime:

Siprofloksasine Bağlı Geç Tip Aşırı Duyarlılık Reaksiyonlarında CD4+ T Hücrelerinin Sitokin Salınımları ve Proliferatif Kapasiteleri

Öz:

Giriş: Siprofloksasin (SPFX), en yaygın kullanılan kinolon grubu antibiyotiklerden olup, kutanöz ters ilaç reaksiyonları oluşturabilme kapasitesine sahiptir. Gecikmiş tip aşırı duyarlılık reaksiyonlarında (ADR) kesin tanı konulması zor olmakla beraber in vitro tanı testlerinin geç tip ilaç ADR’de kullanımı önemlidir. Çalışmamızda SPFX’e bağlı geç tip ADR geçiren hastalarda, ilaçlar ile uyarılmış CD4+T hücrelerinde, hücre içi sitokin üretimleri ve lenfosit transformasyon (LTT) yanıtları araştırılmıştır. Gereç ve Yöntemler: Çalışmaya SPFX ile geç tip hipersensitivite reaksiyonu (n=8) geçiren hastalar ve sağlıklı kontroller (n=10) dâhil edilmiş, intradermal testler ve yama testleri uygulanmıştır. LTT metodu ile SPFX’e özgül CD4+T hücre proliferasyonu belirlenmiştir. SPFX’e özgül CD4+T hücrelerinde hücre içi IL-4, IL-10, IL-2 ve IFN-γ düzeyleri akan hücre ölçer kullanımı ile değerlendirilmiştir. Kültür üst sıvılarındaki sitokin düzeyleri ELISA aracılığı ile ölçülmüştür. Bulgular: Geç tip ADR geçiren hastalarda 5 ve 10 µg/ml SPFX uyarımı CD4+T hücre proliferasyonunu arttırmıştır (p=0.014 ve p=0.05, sırasıyla). IL-2 (p=0.02, p=0.001 ve p=0.001, sırasıyla) ve IL-4 (p=0.001) salgılayan CD4+T hücre yüzdesi artmasına rağmen IFN-γ+(p=0.001, p=0.011 ve p=0.012, sırasıyla) ve IL-10+(p=0.001, p=0.001 ve p=0.002, sırasıyla) CD4+T hücre oranları azalmıştır. Hücre kültür üst sıvılarında SPX uyarımından bağımsız olarak, hastalarda IL-10 düzeyi (p<0.000, p=0.004, p=0.001 ve p=0.0001, sırasıyla) azalırken, IL-4 düzeyi (p=0.003, p=0.013 ve p=0.0001, sırasıyla) artmıştır. İntradermal test uygulanan hastaların sadece birinde pozitif yanıt saptanır iken, yama testlerinde pozitif sonuç elde edilmemiştir. Sonuç: Bulgularımız, IL-2 ve IL-4 üreten CD4+T hücrelerindeki artışla birlikte IL-10 ve IFN-γ üreten CD4+T hücrelerindeki azalmanın, gecikmiş tipte CPFX alerjisine sahip hastalarda DTHR ile ilişkili olduğunu düşündürmektedir. LT ile birlikte hücre içi sitokin ölçümleri, in vivo testlerin negatif kaldıkları, karar verdirici olamadıkları ve hatta uygulanamadıkları durumlarda, gecikmiş tipte CPFX hipersensitivitesinin değerlendirilmesinde fayda sağlayabilir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	ertek b, Demir S, Kucuksezer U, Pur Ozyigit L, Gelincik A, Buyukozturk S, Deniz G, Aktaş E (2020). Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. , 120 - 128. 10.25002/tji.2020.1339
Chicago	ertek belkıs,Demir Semra,Kucuksezer Umut Can,Pur Ozyigit Leyla,Gelincik Aslı,Buyukozturk Suna,Deniz Gunnur,Aktaş Esin Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. (2020): 120 - 128. 10.25002/tji.2020.1339
MLA	ertek belkıs,Demir Semra,Kucuksezer Umut Can,Pur Ozyigit Leyla,Gelincik Aslı,Buyukozturk Suna,Deniz Gunnur,Aktaş Esin Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. , 2020, ss.120 - 128. 10.25002/tji.2020.1339
AMA	ertek b,Demir S,Kucuksezer U,Pur Ozyigit L,Gelincik A,Buyukozturk S,Deniz G,Aktaş E Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. . 2020; 120 - 128. 10.25002/tji.2020.1339
Vancouver	ertek b,Demir S,Kucuksezer U,Pur Ozyigit L,Gelincik A,Buyukozturk S,Deniz G,Aktaş E Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. . 2020; 120 - 128. 10.25002/tji.2020.1339
IEEE	ertek b,Demir S,Kucuksezer U,Pur Ozyigit L,Gelincik A,Buyukozturk S,Deniz G,Aktaş E "Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin." , ss.120 - 128, 2020. 10.25002/tji.2020.1339
ISNAD	ertek, belkıs vd. "Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin". (2020), 120-128. https://doi.org/10.25002/tji.2020.1339

APA	ertek b, Demir S, Kucuksezer U, Pur Ozyigit L, Gelincik A, Buyukozturk S, Deniz G, Aktaş E (2020). Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. Turkish Journal of Immunology, 8(3), 120 - 128. 10.25002/tji.2020.1339
Chicago	ertek belkıs,Demir Semra,Kucuksezer Umut Can,Pur Ozyigit Leyla,Gelincik Aslı,Buyukozturk Suna,Deniz Gunnur,Aktaş Esin Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. Turkish Journal of Immunology 8, no.3 (2020): 120 - 128. 10.25002/tji.2020.1339
MLA	ertek belkıs,Demir Semra,Kucuksezer Umut Can,Pur Ozyigit Leyla,Gelincik Aslı,Buyukozturk Suna,Deniz Gunnur,Aktaş Esin Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. Turkish Journal of Immunology, vol.8, no.3, 2020, ss.120 - 128. 10.25002/tji.2020.1339
AMA	ertek b,Demir S,Kucuksezer U,Pur Ozyigit L,Gelincik A,Buyukozturk S,Deniz G,Aktaş E Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. Turkish Journal of Immunology. 2020; 8(3): 120 - 128. 10.25002/tji.2020.1339
Vancouver	ertek b,Demir S,Kucuksezer U,Pur Ozyigit L,Gelincik A,Buyukozturk S,Deniz G,Aktaş E Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin. Turkish Journal of Immunology. 2020; 8(3): 120 - 128. 10.25002/tji.2020.1339
IEEE	ertek b,Demir S,Kucuksezer U,Pur Ozyigit L,Gelincik A,Buyukozturk S,Deniz G,Aktaş E "Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin." Turkish Journal of Immunology, 8, ss.120 - 128, 2020. 10.25002/tji.2020.1339
ISNAD	ertek, belkıs vd. "Cytokine Secretion and Proliferative Capacity of CD4+ T Cells in Delayed Type Hypersensitivity Reactions due to Ciprofloxacin". Turkish Journal of Immunology 8/3 (2020), 120-128. https://doi.org/10.25002/tji.2020.1339