The role of interleukin-6 gene in distinction of transudate-exudate in pleural effusions

Yıl 2024, Cilt: 49 Sayı: 2, 391 – 399, 30.06.2024

Müge Gülcihan Önal , Hilal Akalın , Armagan Akkuş , Munis Dündar , Ömer Önal

https://doi.org/10.17826/cumj.1441437

Öz

Amaç: Bu çalışma, plevral sıvı örneklerinde IL-6 gen ekspresyonunu değerlendirmeyi ve ekspresyon düzeyleri ile promotör polimorfizmleri arasındaki ilişkiyi inceleyerek plevral efüzyon sınıflandırmasında daha doğru sonuçlar elde etmeyi amaçlamaktadır.
Gereç ve Yöntem: Çalışmaya plevral sıvısı bulunan toplam 38 yetişkin hasta (19 transüda, 19 eksüda) ve 33 sağlıklı kontrol grubu dahil edildi. IL-6 gen ekspresyonu çalışması için, transüda ve eksüda plevral sıvılarından RNA izole edildi ve ekspresyon seviyeleri iki grup arasında karşılaştırıldı. Ardından, kontrol ve hasta gruplarının genomik DNA’larından LightCycler 480 II real-time polimeraz zincir reaksiyonu kullanılarak -174G>C (rs1800795), -572G>C (rs1800796) ve -597G>A (rs1800797) polimorfizmleri analiz edildi.
Bulgular: Eksüda grubunda IL-6 düzeyleri, transüda grubuna göre 7,13 kat daha fazla ifade edildi. Transüda-eksüda grupları arasında polimorfizmler açısından anlamlı bir fark bulunamadı. Ancak transüda-eksüda hasta grupları kontrol grupları ile karşılaştırıldığında, -174G>C polimorfizmi ve -597G>A polimorfizmi istatistiksel olarak anlamlıydı.
Sonuç: Plevral efüzyon tedavisi sıvı karakterizasyonu ile başlar. Zorlu vakalarda, mevcut parametreler yetersizdir. Bulgularımız, geleneksel kriterlerin ötesine geçerek eksüdatif ve transüdatif durumları bağımsız olarak ayırt eden güçlü bir biyobelirteç olarak IL-6 ‘yı işaret etmektedir. IL-6 , plevral efüzyonun hassas karakterizasyonu için umut vermekte olup, patofizyoloji hakkında bilgi sağlayarak hedeflenen tedavi yaklaşımlarına olanak tanımaktadır.

Anahtar Kelimeler

IL-6, mRNA ekspresyonu, plevral efüzyon, genetik polimorfizm

Etik Beyan

Our study was approved by Erciyes University Ethics Committee (No: 2017/262). Erciyes University Ethics Committee approved this project according to the Declaration of Helsinki revised in 2000.

Destekleyen Kurum

Erciyes University Scientific Research Projects Unit (Kayseri, Turkey)

Teşekkür

This study was supported by Erciyes University Scientific Research Projects Unit (Kayseri, Turkey) with the number TDK-2017-7518.

Kaynakça

• Zielinska-Krawczyk M, Krenke R, Grabczak EM, Light RW. Pleural manometry–historical background, rationale for use and methods of measurement. Respir Med. 2018;136:21-8.
• Miserocchi G, Venturoli D, Negrini D, Del Fabbro M. Model of pleural fluid turnover. J Appl Physiol. 1993;75:1798-1806.
• Porcel JM, Light RW. Pleural effusions. Dis Mon. 2013;59:29-57.
• Maldonado F, Lentz RJ, Light RW. Diagnostic approach to pleural diseases: new tricks for an old trade. F1000Res. 2017;6:1135.
• Krishna R, Rudrappa M. Pleural Effusion. Treasure Island, FL; StatPearls Publishing; 2018.
• Feller-Kopman D, Light R. Pleural Disease N Engl J Med. 2018;378:740-51.
• Rosse C, Gaddum-Rosse P. Hollinshead’s Textbook of Anatomy. Baltimore, Lippincott Williams & Wilkins.; 1997.
• Tse HTK, Gossett DR, Moon YS, et al. Quantitative Diagnosis of Malignant Pleural Effusions by Single-Cell Mechanophenotyping. Sci Transl Med. 2013;5:212ra163.
• HEFFNER JE. Diagnosis and management of malignant pleural effusions. Respirology. 2007;13:5-20.
• Bouros D, Pneumatikos I, Tzouvelekis A. Pleural ınvolvement in systemic autoimmune disorders. Respiration. 2008;75:361-71.
• Karkhanis VS, Joshi JM. Pleural effusion: diagnosis, treatment, and management. Emerg Med. 2012;4:31-52.
• Porcel JM, Light RW. Diagnostic approach to pleural effusion in adults. Am Fam Physician. 2006;73:1211-20.
• Antas P, Borchert J, Ponte C, Lima J, Georg I, Bastos M et al. Interleukin-6 and -27 as potential novel biomarkers for human pleural tuberculosis regardless of the immunological status. Microbes Infect. 2024;26:105238.
• Kumar H, Kawai T, Akira S. Pathogen Recognition by the Innate Immune System. Int Rev Immunol. 2011;30:16-34.
• Zamzam MA, Abd El-Aziz AA, El Wahsh RA, Sonbol AA, Abu El Nour SM. Role of interleukin-6 in diagnosis of pleural effusion. Egypt J Chest Dis Tuberc. 2016;65:173-7.
• Shu CC, Wang JY, Hsu CL et al. Diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion. Respirology. 2015;20:147-54.
• Yensey Ç, Aktoğu S, Kalenc S, Onur F. Proinflammatory cytokines: are they usefull in differential diagnosis of pleural effusions? Ege Tıp Dergisi. 2006;45:19-24.
• Yalcin NG, Choong CKC, Eizenberg N. Anatomy and pathophysiology of the pleura and pleural space. Thorac Surg Clin. 2013;23:1-10.
• Diaz-Guzman E, Dweik RA. Diagnosis and management of pleural effusions: a practical approach. Compr Ther. 2007;33:237-46.
• Sertoğullarından B, Dallı A, Ekin S. How should approach to pleural effusion? J Chest Dis Crit Care Med. 2015;2:50-5.
• Heffner JE, Brown LK, Barbieri CA. Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Primary Study Investigators. Chest. 1997;111:970-80.
• Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL. Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of c-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab. 2003;88:255-9.
• Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275:18138-44.
• Rivera-Chavez FA, Peters-Hybki DL, Barber RC, O’Keefe GE. Interleukin-6 promoter haplotypes and interleukin-6 cytokine responses. Shock. 2003;20:218-23.
• Sharma A, Singh K, Biswas A, et al. Impact of interleukin 6 promoter polymorphisms (−174 G>C, −572 G >C and −597 G >A) on plasma IL-6 levels and their influence on the development of DVT: a study from India. Hematology. 2018;23:833-8.
• Boeta-Lopez K, Duran J, Elizondo D, Gonzales E, Rentfro A, Schwarzbach AE et al. Association of interleukin-6 polymorphisms with obesity or metabolic traits in young Mexican-Americans. Obes Sci Pract. 2018;4:85-96.
• Peng X, Shi J, Sun W, Ruan X, Guo Y, Zhao L et al. Genetic polymorphisms of IL-6 promoter in cancer susceptibility and prognosis: a meta-analysis. Oncotarget. 2018;9:12351-64.

The role of interleukin-6 gene in distinction of transudate-exudate in pleural effusions

Yıl 2024, Cilt: 49 Sayı: 2, 391 – 399, 30.06.2024

Müge Gülcihan Önal , Hilal Akalın , Armagan Akkuş , Munis Dündar , Ömer Önal

https://doi.org/10.17826/cumj.1441437

Öz

Purpose: This study aims to appraise IL-6 gene expression in pleural fluid samples and establish a connection between expression levels and promoter polymorphisms for more accurate pleural effusion classification.
Materials and Methods: A total of 38 adult patients (transudate (19) and exudate (19)) with pleural fluid and 33 healthy controls were included in the study. For the IL-6 gene expression study, RNA was isolated from transudate and exudate pleural fluids, and expression levels were compared between the two groups. Then, -174G>C (rs1800795), -572G>C (rs1800796) and, -597G>A (rs1800797) polymorphisms were analyzed using LightCycler® 480 II with real-time polymerase chain reaction from genomic DNA of controls and patients.
Results: IL-6 levels were 7.13-fold more expressed in the exudate group than in the transudate group. No significant difference was found between the transudate-exudate groups in terms of polymorphisms. However, when we compared the transudate-exudate patient groups with the control groups, -174 G>C polymorphism and -597 G>A polymorphism were statistically significant.
Conclusion: Pleural effusion treatment initiates with fluid characterization. In challenging cases, the current parameters are inadequate. Our findings indicate that IL-6 is a robust biomarker, independently distinguishing exudative and transudative states, surpassing traditional criteria. IL-6 shows promise for precise pleural effusion characterization, offering insights into pathophysiology and enabling targeted therapeutic interventions.

Anahtar Kelimeler

IL-6, mRNA Expression, Pleural Effusion, Genetic Polymorphism

Kaynakça

• Zielinska-Krawczyk M, Krenke R, Grabczak EM, Light RW. Pleural manometry–historical background, rationale for use and methods of measurement. Respir Med. 2018;136:21-8.
• Miserocchi G, Venturoli D, Negrini D, Del Fabbro M. Model of pleural fluid turnover. J Appl Physiol. 1993;75:1798-1806.
• Porcel JM, Light RW. Pleural effusions. Dis Mon. 2013;59:29-57.
• Maldonado F, Lentz RJ, Light RW. Diagnostic approach to pleural diseases: new tricks for an old trade. F1000Res. 2017;6:1135.
• Krishna R, Rudrappa M. Pleural Effusion. Treasure Island, FL; StatPearls Publishing; 2018.
• Feller-Kopman D, Light R. Pleural Disease N Engl J Med. 2018;378:740-51.
• Rosse C, Gaddum-Rosse P. Hollinshead’s Textbook of Anatomy. Baltimore, Lippincott Williams & Wilkins.; 1997.
• Tse HTK, Gossett DR, Moon YS, et al. Quantitative Diagnosis of Malignant Pleural Effusions by Single-Cell Mechanophenotyping. Sci Transl Med. 2013;5:212ra163.
• HEFFNER JE. Diagnosis and management of malignant pleural effusions. Respirology. 2007;13:5-20.
• Bouros D, Pneumatikos I, Tzouvelekis A. Pleural ınvolvement in systemic autoimmune disorders. Respiration. 2008;75:361-71.
• Karkhanis VS, Joshi JM. Pleural effusion: diagnosis, treatment, and management. Emerg Med. 2012;4:31-52.
• Porcel JM, Light RW. Diagnostic approach to pleural effusion in adults. Am Fam Physician. 2006;73:1211-20.
• Antas P, Borchert J, Ponte C, Lima J, Georg I, Bastos M et al. Interleukin-6 and -27 as potential novel biomarkers for human pleural tuberculosis regardless of the immunological status. Microbes Infect. 2024;26:105238.
• Kumar H, Kawai T, Akira S. Pathogen Recognition by the Innate Immune System. Int Rev Immunol. 2011;30:16-34.
• Zamzam MA, Abd El-Aziz AA, El Wahsh RA, Sonbol AA, Abu El Nour SM. Role of interleukin-6 in diagnosis of pleural effusion. Egypt J Chest Dis Tuberc. 2016;65:173-7.
• Shu CC, Wang JY, Hsu CL et al. Diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion. Respirology. 2015;20:147-54.
• Yensey Ç, Aktoğu S, Kalenc S, Onur F. Proinflammatory cytokines: are they usefull in differential diagnosis of pleural effusions? Ege Tıp Dergisi. 2006;45:19-24.
• Yalcin NG, Choong CKC, Eizenberg N. Anatomy and pathophysiology of the pleura and pleural space. Thorac Surg Clin. 2013;23:1-10.
• Diaz-Guzman E, Dweik RA. Diagnosis and management of pleural effusions: a practical approach. Compr Ther. 2007;33:237-46.
• Sertoğullarından B, Dallı A, Ekin S. How should approach to pleural effusion? J Chest Dis Crit Care Med. 2015;2:50-5.
• Heffner JE, Brown LK, Barbieri CA. Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Primary Study Investigators. Chest. 1997;111:970-80.
• Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL. Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of c-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab. 2003;88:255-9.
• Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275:18138-44.
• Rivera-Chavez FA, Peters-Hybki DL, Barber RC, O’Keefe GE. Interleukin-6 promoter haplotypes and interleukin-6 cytokine responses. Shock. 2003;20:218-23.
• Sharma A, Singh K, Biswas A, et al. Impact of interleukin 6 promoter polymorphisms (−174 G>C, −572 G >C and −597 G >A) on plasma IL-6 levels and their influence on the development of DVT: a study from India. Hematology. 2018;23:833-8.
• Boeta-Lopez K, Duran J, Elizondo D, Gonzales E, Rentfro A, Schwarzbach AE et al. Association of interleukin-6 polymorphisms with obesity or metabolic traits in young Mexican-Americans. Obes Sci Pract. 2018;4:85-96.
• Peng X, Shi J, Sun W, Ruan X, Guo Y, Zhao L et al. Genetic polymorphisms of IL-6 promoter in cancer susceptibility and prognosis: a meta-analysis. Oncotarget. 2018;9:12351-64.

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