Comportamento anti-inflamatório da IL-6 nos derrames pleurais pós-revascularização do miocárdio*

IL-6 anti-inflammatory activity in pleural effusion post-coronary artery bypass graft surgery*

 

António M S Chibante¹

Marcelo C Vaz²

Francisco Suzo Vargas³

 

Resumo

Introdução: O comportamento pleural pós-cirurgia de revascularização do miocárdio (PCRM) não está devidamente esclarecido em relação à resposta inflamatória local e requer maior interesse por ser uma observação constante e ainda pouco estudada.

Objectivo: Avaliar o comportamento de algumas citocinas, em especial o possível papel anti-inflamatório da IL-6 ( proteína envolvida na síntese da cortisona), no líquido pleural PCRM, uma vez que a sua actividade pró-inflamatória é constantemente referida, assim como o seu papel de citocina de fase de resposta aguda ao lado do TNF-á e da IL-1â nos processos inflamatórios agudos.

Casuística e método: foram estudadas e analisadas pelo método ELISA as citocinas TNF-á, IL-1â, IL-2, IL-6, IL-8, VEGF e TGF-â em 16 transudatos e 43 exsudatos de líquido pleural em três tempos da fase aguda (2, 24 e 48 horas) PCRM no Instituto do Coração e Serviço de Pneumologia da USP – Brasil.

Resultados: Tanto o TNF-á como IL-2 não sofreram qualquer tipo de elevação dos seus níveis enquanto os da IL-1â só se elevaram a partir das 24 horas, o que coincidiu com a queda da curva da citocina anti-inflamatória TGF-â, que desde o início foi caindo flagrantemente até aos valores dos transudatos. A IL-8 permaneceu elevada nas três fases e o VEGF foi ascendendo os seus níveis, que permaneceram estáveis nas 24 e 48 horas seguintes. A IL-6 mostrou-se em concentrações elevadas desde o início, apresentando-se como a única citocina com potencial anti-inflamatório durante as três fases de avaliação.

Conclusões: Concluímos que a citocina IL-6 parece ter papel anti-inflamatório de destaque e superior ao TGF-â nos derrames pleurais PCRM e que o seu comportamento desarticula, pelo menos neste tipo de derrame, a ideia de citocina pró-inflamatória de resposta de fase aguda. Ao que parece, este é o primeiro estudo que procura demonstrar um papel favorável da IL-6 no processo inflamatório da pleura na fase aguda PCRM.

Palavras-chave: IL-6, citocinas, derrame pleural.

 

 

Abstract

Introduction: The local inflammatory reaction aspects of pleural behaviour post-coronary artery bypass graft surgery (PCABG) are not completely evident, demanding further study and observation.

Aim: To evaluate the behaviour of some cytokines and the possible anti-inflammatory activity of IL-6 (a protein involved in cortisone synthesis) on acute PCABG pleural fluid, since this cytokine is usually considered as an acute phase reaction protein associated to high concentrations of TNF-alpha and IL-1beta in immediate inflammatory reactions.

Material and methods:The concentrations of the TNFalpha, IL-1beta, IL-2, IL-6, IL-8, VEGF and TGF-beta cytokines in 16 transudates and 43 exudates in acute PCABS pleural fluid of patients were analysed by the ELISA method 2, 24 and 48 hours after surgery at the Instituto do Coração and Serviço de Pneumologia da USP, Brazil.

Results: While no increase was seen in either TNFalpha or IL-2 in any of the three tests, IL-1beta increased after 24 until 48 hours, coinciding with the TGFbeta curve decline which fell from the beginning to reach the transudates levels. IL-8 reminded higher from the beginning and through the two subsequent tests while VEGF levels were elevated from the first test and continued high for the following 24 and 48 hours. IL-6 had high concentrations from the beginning, suggesting an anti-inflammatory activity at the three times of testing.

Conclusions: We conclude that IL-6 seems to play an important anti-inflammatory part which is superior to the anti-inflammatory activity of TGF-beta in PCABG pleural effusions. This performance of IL-6 breaks with the traditional idea of it being a pro-inflammatory acute phase reaction cytokine, at least in this type of pleural effusion. This seems to be the first study involving the favourable behaviour of IL-6 in the inflammatory reaction of pleura in the acute phase of PCABG surgery.

Key-words: IL-6, pleural effusion, coronary artery bypass graft surgery.

 

 

Texto completo disponível apenas em PDF.

Full text only available in PDF format.

 

 

Bibliografia / Bibliography

1. Ishikawa S, Takahashi T, Ohtaki A, Sato Y, Suzuki M, Hasegawa Y, Mohara J, Oshima K Morishita Y. Peripheral pulmonary atelectasis and oxygentation impairment following coronary artery bypass grafting. J Cardiovasc Surg (Torino) 2002;43:419.        [ Links ]

2. Vargas FS, Vezhimi KK, Jatene FF, Terra-Filho M, Hueb W, Cukier A, Light RW. Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization. Rev Hosp Clin Fac Med São Paulo 2002;57:135-42.

3. Light RW. Pleural effusions after coronary artery bypass graft surgery. Curr Opin Pulm Med 2002;8:308-11.

4. Ishikawa S, Ohtaki A, Takahashi T, Sakate K, Koyano T, Kano M, Ohkis S, Kawashima O, Hamada Y, Moorishita Y. PEEP therapy for patients with pleurotomy during coronary artery bypass. J Card Surg 2000;15:175-8.

5. Light RW, Rogers JT, Cheng D et al. Large pleural effusions after coronary artery bypassing grafting. Cardiovascular Surgery Associates 1999;130:891-6.

6. Lee YC, Vaz Mac, Ely KA et al. Symptomatic persistent post-coronary artery bypass graft pleural effusion requiring treatment-clinical and histologic features. Chest 2001;119:795-800.

7. Areno JP, McCarteney JP, Eggerstedt J, Grafton W, George R. Persistent pleural effusions following coronary bypass surgery. Chest 1998;114:311-4.

8. Wan S, Marchant A, Desemet JM. Human cytokine responses to cardiac transplantation and coronary artery bypass grafting. J Thorac Cardiovasc Surg 1996; 111:469-77.

9. Gaudino M, Zamparelli R, Andreotti F, Burzotta F, Tacoviello L, Glieca F, Benedett M, Maseri A, Schiavello R, Possati G. Normothermia does not improve postoperative hemostasis nor does it reduce inflammatory activation in patients undergoing primary isolated coronary artery bypass. J Thorac Cardiovasc Surg 2002;123:1092-100.

10. Dinarello CA. Proinflammatory Cytokines. Chest 2000;118:503-8.

11. Kroegel C, Anthony VB. Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. Eur Respir J 1997;10:2411-18.

12. Xirouchaki MD, Tzanakis N, Bouros D, Kyriakou D, Karkavirtsas N, Alexandrakis M, Siafakas NM. Diagnostic value of interleukin-1a, interleukin-6 and tumor necrosis factor in pleural effusions. Chest 2002;121:815-20.

13. Opal SM, De Pablo VA. Anti-inflammatory cytokines. Chest 2000;117:1162-72.

14. Alexandrakis MG, Kuriakou DS, Bouros D, Xylouri I, Antonakis N, Siafakas NM. Interleukin-6 and its relationships to acute phase proteins in serous effusion differentiation. Oncol Respir. 2001;8:415-20.

15. Zhang GJ, Adachi I. Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res 1999;19:2BB 1427-32.

16. Barton BE. IL-6: insights into novel biological activities. Clin Immunol 1997; 85:16-20.

17. Monton C, Torres A. Lung inflammatory response in pneumonia. Arch Chest Dis 1998;53:56-63.

18. Yokoyama A, Kohno N, Fujino A, Abe M, Ishida O, Hiwada K. Soluble interleukin-6 receptor levels in pleural effusions. Respir Med 1996;90:329-32.

19. Stites D P, Terr AL, Parslow TG. Medical Immunology. 9ed. Stamford: CT, Appleton and Lange, 1997.

20. Tilg H, Trehu E, Atkins MB. Interleukin-6 as an antiinflammatory cytokine: reduction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor. Blood 1994;83:113-8.

21. Ruzek MC, Miller AH, Opal SM. Caracterization of early cytokine responses in an interleukin-6 dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection. J Exp Med 1997; 185:1185-92.

22. Xing Z,Gauldie J, Cox G et al. Il-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101:311-20.

23. Gary-Lee YC, Lane KB. The many faces of transforming growth factor- beta in pleural diseases. Curr Opin Pulm Med 2001; 7:173-9.

24. Grove CS, Lee YC. Vascular endothelial growth factor: the key mediator in pleural effusion formation. Curr Opin Pulm Med 2002;8:294-301.

25. Nasreen N, Mohammed KA, Hardwick J, Van Horn RD, Sanders KL, Doerschuk CM, Hott JW, Antony VB. Polar production of IL-8 by mesothelial cells promotes the transmesothelial immigration of neutrophil: role of intercellular adhesion molecule-1. J Infect Dis 2001; 183:1683-45.

26. Weissflog D, Kroegel C, Luttmann W, Grahmann PR, Hasse J. Leukocyte infiltration and secretion of cytokines in pleural drainage fluid after thoracic surgery: impaired cytokine response in malignancy and postoperative complications. Chest 1999;115:1604-10.

27. Vaz MAC, Chibante AMS, Vargas FS. Cytokines in Pleural Effusions in First 48 hours after Coronary Artery Bypass Surgery (CABG). Chest 2004;126:8965-8969S.

 

* Trabalho realizado no Serviço de Pneumologia da Universidade de São Paulo e no Instituto do Coração. / Study undertaken at the Universidade de São Paulo Pulmonology Unit and Universidade de São Paulo Heart Institute.

¹ Professor Associado de Pneumologia da Universidade Federal do Estado do Rio de Janeiro / Associate Professor of Pulmonology, Universidade Federal do Estado do Rio de Janeiro

² Professor Assistente de Pneumologia da Universidade de São Paulo / Assistant Professor of Pulmonology, Universidade de São Paulo

³ Professor Titular de Pneumologia da Universidade de São Paulo / Full Professor of Pulmonology, Universidade de São Paulo

 

Correspondência/Correspondence to:

Rua Sorocaba 477/601 - CEP 22271-110 Botafogo RJ

Rio de Janeiro - BRASIL Fone/Fax 55.21.2430-8854

E-mail - chibante@domain.com.br / chibante@gmail.com

 

Recebido para publicação/received for publication: 06.12.09

Aceite para publicação/accepted for publication: 07.03.01