Tüberküloz plörezide spesifik koruyucu immün yanıtın değerlendirilmesi
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Date
2006
Authors
Budak, Ferah
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Dünyada önemli bir problem olmaya devam eden tüberküloz (TB)’un kontrolü ve gelecekte eradikasyonu için etkili aşılara, spesifik tanı reaktiflerine; tedavisi için de alternatif immün modülatör yaklaşımların belirlenmesine ihtiyaç vardır. Çalışmamızda, TB aşısı için aday peptidler olarak kabul edilen CFP-10 ve ESAT- 6’nın koruyucu immün cevaptaki rolü ile TB’da lokal koruyucu immün cevapta yer alan sitokin ve mononükleer hücrelerin etkinliği araştırıldı. Bu amaçla TB plörezi (hasta grubu) ve malign plörezili (kontrol grubu) hastalardan elde edilen plevral sıvı mononükleer hücreleri PHA, PPD, CFP-10 ve ESAT-6 ile stimüle edilerek intrasellüler ve ekstrasellüler sitokin düzeyleri (IFN-γ, IL-10, IL-13, IL-4) değerlendirildi. Ayrıca hasta ve kontrol gruplarında plevra sıvısı IFN-γ, IL-12p40, IL-18, IL-8, TNF-α, IL-4, IL-10, IL-13, sFas, sFasL düzeyleri ile mononükleer hücre oranları araştırıldı. Plevra sıvısı mononükleer hücrelerinin CFP-10 ve ESAT-6 ile stimülasyonu sonucu, TB plörezi olgularında ekstrasellüler ve intrasellüler IFN-γ düzeylerinde, kontrol grubuna göre belirgin artış olduğu, antienflamatuvar bir sitokin olan IL-10 düzeylerinin de arttığı saptandı. TB plörezili hastalarda plevra sıvısı IFN-γ, IL-12p40, IL-18, IL-8, TNF-α düzeyleri, kontrol gruplarına göre yüksek bulundu. Elde edilen veriler ışığında TB’daki koruyucu immünitede Th1 tipi spesifik hücresel immünitenin primer yanıt olduğu; ESAT-6 ve CFP-10’un TB plörezili olgularda bu yanıtı endükledikleri; bu peptitlerin TB aşı preparasyonlarında yer almaları sonucu koruyucu etkinliği daha güçlü aşıların geliştirilebileceği; ESAT-6 ve CFP-10’un yer aldığı testlerden BCG’ye bağlı Tüberkülin pozitifliği ile doğal enfeksiyonun ayrımında ve özellikle TB’un endemik olmadığı bölgelerde tanıda yararlanılabileceği; ayrıca plevra sıvısındaki IFN-γ düzeylerinin TB plörezi ve malign plörezi ayırımda kullanılabileceği sonucuna varıldı.
There are requirements for effective vaccines and specific diagnostic reagents to control and eradicate Tuberculosis (TB) which remains an important health problem. Alternative immunomodulatory approaches also needs to be developed for better treatment of the disease. In our study, the roles of ESAT and CFP-10, which are candidate peptides for new TB vaccine preparations, and effectiveness of cytokines and mononuclear cells were investigated to determine their involvement in local protective immune response. For this aim, pleural fluid mononuclear cells obtained from TB pleurisy (study group) and malign pleurisy or non-TB non-malign pleurisy (control groups) patients were stimulated with PHA, PPD, ESAT-6 and CFP-10 prior to the measurement of intracellular and extracellular cytokines (IFN-γ, IL-4, IL-10 and IL-13). Additionally, the levels of IFN-γ, IL-4, IL-8, IL-10, IL-12p40, IL-13, TNF-α, sFas and sFasL, and the proportional profiles of mononuclear cell subsets in pleural fluids were evaluated. As a result of stimulation of pleural fluid mononuclear cells with ESAT-6 and CFP-10, extracellular and intracellular levels of IFN-γ dramatically increased in TB pleurisy cases when compared to control groups, and the levels of anti-inflammatory cytokine IL-10 were also determined to be elevated. It was also shown that levels of pleural fluid IFN-γ, IL-8, IL-12p40, IL-18, TNF-α and sFasL were significantly higher in the patients with TB pleurisy in comparison to control groups. In the light of the data obtained in our study it can be suggested that Th1 type specific cellular immunity is the primary response responsible for protective immunity in TB; that more potent vaccines may be developed by including ESAT-6 and CFP-10 in new vaccine preparations since these peptides induce protective response providing selfcontrol of TB pleurisy; that diagnostic tests using ESAT-6 and CFP-10 could be used to distinguish natural infection from Tuberculin test positivity due to previous BCG vaccination and to diagnose TB in the regions where TB is not endemic; and additionally, that the measurements of pleural fluid IFN-γ levels might be used to differ TB pleurisy and malign pleurisy.
There are requirements for effective vaccines and specific diagnostic reagents to control and eradicate Tuberculosis (TB) which remains an important health problem. Alternative immunomodulatory approaches also needs to be developed for better treatment of the disease. In our study, the roles of ESAT and CFP-10, which are candidate peptides for new TB vaccine preparations, and effectiveness of cytokines and mononuclear cells were investigated to determine their involvement in local protective immune response. For this aim, pleural fluid mononuclear cells obtained from TB pleurisy (study group) and malign pleurisy or non-TB non-malign pleurisy (control groups) patients were stimulated with PHA, PPD, ESAT-6 and CFP-10 prior to the measurement of intracellular and extracellular cytokines (IFN-γ, IL-4, IL-10 and IL-13). Additionally, the levels of IFN-γ, IL-4, IL-8, IL-10, IL-12p40, IL-13, TNF-α, sFas and sFasL, and the proportional profiles of mononuclear cell subsets in pleural fluids were evaluated. As a result of stimulation of pleural fluid mononuclear cells with ESAT-6 and CFP-10, extracellular and intracellular levels of IFN-γ dramatically increased in TB pleurisy cases when compared to control groups, and the levels of anti-inflammatory cytokine IL-10 were also determined to be elevated. It was also shown that levels of pleural fluid IFN-γ, IL-8, IL-12p40, IL-18, TNF-α and sFasL were significantly higher in the patients with TB pleurisy in comparison to control groups. In the light of the data obtained in our study it can be suggested that Th1 type specific cellular immunity is the primary response responsible for protective immunity in TB; that more potent vaccines may be developed by including ESAT-6 and CFP-10 in new vaccine preparations since these peptides induce protective response providing selfcontrol of TB pleurisy; that diagnostic tests using ESAT-6 and CFP-10 could be used to distinguish natural infection from Tuberculin test positivity due to previous BCG vaccination and to diagnose TB in the regions where TB is not endemic; and additionally, that the measurements of pleural fluid IFN-γ levels might be used to differ TB pleurisy and malign pleurisy.
Description
Keywords
Tüberküloz plörezi, Mycobacterium tuberculosis, ESAT-6, CFP-10, Sitokin, Tuberculous pleurisy, Cytokine
Citation
Budak, F. (2006). Tüberküloz plörezide spesifik koruyucu immün yanıtın değerlendirilmesi. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.