Immünomodülatör özellikteki yeni sitokinlerin Bruselloz enfeksiyonlarında değerlendirilmesi
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Date
2019
Authors
Hız, Pınar
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Bruselloz dünya çapında yaygın olarak görülen zoonotik bir hastalıktır ve Brucella bakterisi ile konak arasındaki etkileşimler hastalığın seyri açısından oldukça önemlidir. Sitokinler anti-bakteriyel immünitede rol oynayan önemli mediatörlerdir. Günümüzde tanımlanmış yeni sitokin grupları birçok farklı hastalık modelinde immünomodülatör özellikleri açısından değerlendirilmiştir. Bu yeni sitokin grupları ile bruselloz hastalığı arasındaki bağlantıya dair henüz bir çalışma bulunmamaktadır. Çalışmanın amacı, yeni immünomodülatör sitokin gruplarının (IL-35, IL-36, IL-37, IL-38, IL-39) Brucella enfeksiyonlarında değerlendirilmesi ve hastalığın kronikleşmeye gidişindeki etkilerinin incelenmesidir. Bu çalışmada, yeni sitokin gruplarının (IL-35, IL-36, IL-37, IL-38, IL-39) bruselloz enfeksiyonundaki etkinliği, serolojik ve moleküler yöntemler kullanılarak incelenmiştir. Çalışma için, 40 sağlıklı kontrol, 40 akut ve 40 kronik bruselloz hastasından 20'şer ml kan örneği alınmıştır. Hasta ve sağlıklı kontrollerin serumlarındaki IL-35, IL-36, IL-37, IL-38 ve IL-39 sitokin seviyeleri Enzyme Linked Immunosorbent Assay (ELISA) yöntemi ile tespit edilmiştir. Periferik kan mononükleer hücre (PKMH)'lerinde ise bu sitokinleri belirleyen transkripsiyon faktörlerinin ekspresyonları gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) ile çalışılmıştır. Çalışmamızda her bir sitokin grubuna ait genlerin (Ebi3/IL-12A, IL-36G, IL-37, IL1F10, Ebi3/IL-23A) ekspresyon seviyelerinde anlamlı bir farklılık saptanmazken, hem pro-enflamatuvar (IL-36, IL-39) hem de anti-enflamatuvar (IL-35, IL-37, IL-38) özellikteki sitokinlerin serum düzeylerinin, hasta gruplarında sağlıklı kontrollere oranla azaldığı görülmüştür. Bu durum Brucella bakterisinin bu sitokin gruplarının ekspresyonunu baskıladığını düşündürmektedir. IL-35 ve IL-37 sitokin seviyeleri kronik grupta akut gruba göre anlamlı olarak artmıştır. Anti-enflamatuvar özellikteki bu sitokinlerin kronik vakalarda artmış olması hastalığın kronikleşmeye gidişinde önemli rol oynayabileceklerini düşündürmektedir.
Brucellosis is a common zoonotic disease worldwide and interactions between Brucella and host are very important for the course of the disease. Cytokines are important mediators involved in anti-bacterial immunity. Recently defined new cytokine groups have been evaluated in terms of immunomodulatory properties in many different disease models. There is no study on the relationship between these new cytokine groups and brucellosis. The aim of the study was to evaluate the new immunomodulatory cytokine groups (IL-35, IL-36, IL-37, IL-38, IL-39) in Brucella infections and to investigate the effects of the disease on the course of chronicity. In this study, the effectiveness of new immunomodulatory cytokine groups (IL-35, IL-36, IL-37, IL-38, IL-39) in the process of Brucella infection was investigated by using serological and molecular methods. For this study, 20 ml each blood samples were taken from 40 healthy control, 40 acute and 40 chronic brucellosis patients. The control and patient groups were included in the study by taking into consideration the mean age and exclusion criteria in the consent form. IL-35, IL-36, IL-37, IL-38 and IL-39 cytokine levels in the sera of the patient and healthy controls were determined by ELISA. Expressions of the transcription factors determining these cytokines in peripheral blood mononuclear cells (PBMC) were studied by RT-PCR. In our study, no significant difference was found in the expression levels of the genes of each cytokine group (Ebi3 / IL-12A, IL-36G, IL-37, IL1F10, Ebi3 / IL-23A). Serum levels of both pro-inflammatory (IL-36, IL-39) and anti-inflammatory (IL-35, IL-37, IL-38) cytokines were found to decrease in patient groups compared to healthy controls. This suggests that Brucella suppress the expression of these cytokine groups. IL-35 and IL-37 cytokine levels were significantly increased in the chronic group compared to the acute group. The increase in these anti-inflammatory cytokines in chronic cases suggests that they may play an important role in the progression of the disease to chronicity.
Brucellosis is a common zoonotic disease worldwide and interactions between Brucella and host are very important for the course of the disease. Cytokines are important mediators involved in anti-bacterial immunity. Recently defined new cytokine groups have been evaluated in terms of immunomodulatory properties in many different disease models. There is no study on the relationship between these new cytokine groups and brucellosis. The aim of the study was to evaluate the new immunomodulatory cytokine groups (IL-35, IL-36, IL-37, IL-38, IL-39) in Brucella infections and to investigate the effects of the disease on the course of chronicity. In this study, the effectiveness of new immunomodulatory cytokine groups (IL-35, IL-36, IL-37, IL-38, IL-39) in the process of Brucella infection was investigated by using serological and molecular methods. For this study, 20 ml each blood samples were taken from 40 healthy control, 40 acute and 40 chronic brucellosis patients. The control and patient groups were included in the study by taking into consideration the mean age and exclusion criteria in the consent form. IL-35, IL-36, IL-37, IL-38 and IL-39 cytokine levels in the sera of the patient and healthy controls were determined by ELISA. Expressions of the transcription factors determining these cytokines in peripheral blood mononuclear cells (PBMC) were studied by RT-PCR. In our study, no significant difference was found in the expression levels of the genes of each cytokine group (Ebi3 / IL-12A, IL-36G, IL-37, IL1F10, Ebi3 / IL-23A). Serum levels of both pro-inflammatory (IL-36, IL-39) and anti-inflammatory (IL-35, IL-37, IL-38) cytokines were found to decrease in patient groups compared to healthy controls. This suggests that Brucella suppress the expression of these cytokine groups. IL-35 and IL-37 cytokine levels were significantly increased in the chronic group compared to the acute group. The increase in these anti-inflammatory cytokines in chronic cases suggests that they may play an important role in the progression of the disease to chronicity.
Description
Keywords
Bruselloz, İmmünomodülatör sitokin, Akut, Kronik, Brucellosis, İmmunomodullatory cytokine, Acute, Chronic
Citation
Hız, P. (2019). Immünomodülatör özellikteki yeni sitokinlerin Bruselloz enfeksiyonlarında değerlendirilmesi. Yayınlanmamış doktora tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.