Çiğdem YENİSEY, Serir AKTOĞU, Sabri KALENCİ, F. Onur ERER

Proinflammatory cytokines: Are they usefull in differential diagnosis of pleural effusions?

Interlökin 1-beta (IL-1(3), interlökin-6 (IL-6) ve tümör nekroz faktörü-alfa (TNF-a) , bu sitokinlerin tanısal kullanımını değerlendirmek amacı ile, 128 hastanın plevral sıvısında ölçüldü. Çalıştığımız hasta grubunda 42 hastanın malign, 23 hastanın parapnömanik, 38 hastanın tüberküloz ve 25 hastanın transudatif plevral effüzyonu vardı. Hasta örnekleri Yenişehir Suat Seren Göğüs Hastalıkları Hastanesinde 9B ve 4B kliniklerinde yatan hastalardan sağlandı. Sitokinler IMMULATE 2000 hormon otoanalizöründe BIODPC ticari kitleri yoluyla ölçüldü. Eksudatif serum ve plevral sıvı örnekleri arasındaki IL-1/3, I L-6 ve TNF-a düzeyleri arasındaki fark istatistiksel açıdan önemli bulundu. Transudatif örneklerde, plevra ve serum düzeyleri arasında sadece IL-6 düzeylerindeki fark önemli bulundu. IL-6 ve TNF-a'nın ortalama değerleri her üç grupta da plevral sıvılarda, seruma kıyasla daha yüksek ve anlamlı bulundu (malign, parapnömanik ve tüberküloz). Fakat, en yüksek IL-6 ve TNF-a düzeyleri tüberküloz grubunda saptandı. Souç olarak, düşük serum IL-6 ve yüksek plevral sıvı IL-6 düzeyleri kalp yetmezliği nedeni ile oluşan transüdaları, eksüdalardan ayırmaktadır. Aynı zamanda, serum ve plevral IL-6 en yaygın görülen iki tip eksudanın (tüberküloz ve malignant) tümüyle ayrılmasında kullanılabilir ve serum ve plevradaki TNF-a düzeyleri tüberküloz ve malign effüzyonlarm ayırıcı tanısının desteklenmesinde yararlı olabilir.

Anahtar Kelimeler:

Plevral efüzyon, Sitokinler, Tüberküloz, Tanı, ayırıcı, Eksuda ve transüdalar

Proinflamatuar sitokinler: Plevral effüzyonların ayrımlanmasında yararlımıdır?

Interleukin 1- beta (IL-1(3), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF- a) were measured in pleural fluid from 128 patients with pleural effusion in order to evaluate the diagnostic utility of these cytokines. We studied 42 patients with malignant, 23 patients with parapneumonic, 38 patients with tuberculous, and 25 patients with transudative pleural effusion. Patients samples were taken applied to the Yenişehir Suat Seren Chest Hospital at the clinics 9B an 4B were diagnosed suffereing from pleural effusion. Cytokines were measured by chemiluminescent enzyme immunometric assay using BIODPC commercial kits via IMMULATE 2000 hormone analyzer. In exudative samples the difference between the pleural fluid and serum, IL-ip, IL-6, and TNF-a levels were found statistically important. Only, IL-6 levels were found dramatically different between serum and pleural fluid in transudative samples. Mean IL-6 and TNF-a levels were significantly higher in pleural fluid than in serum in all three groups of patients (malignant, parapneumonic, and tuberculosis). But, the highest mean level of IL-6 and TNF-a were found in tuberculous pleural fluid. In conclusion, low serum IL-6 and high pleural fluid IL-6 can distinguish transudates due to heart failure from exudates. Also, serum and pleural fluid IL-6 could be useful as a complementary marker in the differential diagnosis of two most common types of exudates (tuberculous and malignant) and TNF-a in the serum and pleural fluid could be useful confirmation differential diagnosis of tuberculous and malignant effusions.

Keywords:

Pleural Effusion, Cytokines, Tuberculosis, Diagnosis, Differential, Exudates and Transudates,

PDF

___

1. Antony VB, Godbey SW, Kunkel SL, et al (1993) Recruitment of inflammatory cells to the pleural space: chemotactic cytokines, IL-8, a/id monocyte chemotactic peptide-1 in human pleural fluids. J Immunol 1993; 151:7216-7223.
2. Sahn SA. State of the art: the pleura. Am Rev Respir Dis 1988;138:184-234.
3. Light RW .Useful tests on the pleural fluid in the management of patients with pleural effusions. Curr Opin Pulm Med 1999;5:245-249.
4. Romero S, Martinez A, Hernandez L, et al. Light's criteria revisited: consistency and comparison with new proposed alternative criteria for separating pleural transudates from exudates. Respiration 2000; 67:18-23.
5. Marel M, Stastny B, Melinova L, et al. Diagnosis of pleural effusions: experience with clinical studies, 1986 to 1990. Chest 1995:107:1598-1603.
6. van Deuren, M, Dofferhoff, AS, van der Meer, JW (1992) Cytokines and the response to infection. J Pathol 168,349-356.
7. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest 2000; 117:1162-1172
8. Nicod, LP. Cytokines: Overview. Thorax 1993; 48:660-667.
9. Elias JA, Freundlich B, Kern JA, et al. Cytokine networks in the regulation of inflammation and fibrosis in the lung. Chest 1990; 97:1439-1445.
10. Niebauer J. Inflammatory mediators in heart failure. Int J Cardiol 2000; 72:209-213.
11. Alexandrakis MG, Coulocheri SA, Bouros D, et al. Evaluation of inflammatory cytokines in malignant and benign pleural effusions. Oncol Rep 2000; 7:1327-1332.
12. Hoheisel G, Izbicki G, Roth M, et al. Proinflammatory cytokine levels in patients with lung cancer and carcinomatous pleurisy.Respiration 1998; 65:183-186.
13. Hoheisel G, Izbicki G, Roth M, etal. Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy. Respir Med 1998; 92:14-17.
14. Barnes PF, Fong SJ, Brennan PJ, et al. Local production of tumor necrosis factor and IFN- in tuberculous pleuritis. J Immunol 1990; 145:149-154.
15. Shimokata K, Saka H, Murate T, et al. Cytokine content in pleural effusion: comparison between tuberculous and carcinomatous pleurisy. Chest 1991; 99:1103-1107.
16. Yokoyama A, Kohno N, Fujino S, et al. Soluble interleukin-6 receptor levels in pleural effusions. Respir Med 1996; 90:329-332.
17. Akarsu S, Citak Kurt N, Doğan Y, et al. The differential diagnostic values of cytokine levals in pleural effusion. Mediators of Inflammation 2005; 1: 2-8.
18. Fang-Chi L, Yi-Chu C, Funn-Juh C, Shi-Chuan C. Cytokines and fibrinolytic enzymes an tuberculous and parapneumonic effusions. Clin Immunol 2005; 116(2): 166-173.
19. Xirouchaki N, Tzanakis N, Bouros D, et al. Diagnostic value of interleukin -1a, interleukin-6, and tumor necrosis factor in pleural effusion. Chest 2002; 121:815-820.
20. Castell JV, Gomez-Lechon MJ, David M, et al. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 1990; 12:1179-1186.
21. Lin CC, Liu CC, Lin CY. Changes in cell population and tumor necrosis factor, interleukin-6, and interleukin-8 in malignant pleural effusions after treatment with intrapleural tetracycline. Am Rev Respir Dis 1993; 147:1503-1506.
22. Alexandrakis MG, Coulocheri SA, Bouros D, etal. Evaluation of ferritin, interleukin-6, interleukin-8 and tumor necrosis factor-a in the differentiation of exudates and transudates in pleural effusions. Anticancer Res 1999; 19:3607-3612.
23. Yokoyama A, Maruyama M, Ito M, et al. Interleukin-6 activity in pleural effusion: its diagnostic value and thrombopoietic activity. Chest 1992; 102:1055-1059
24. Agrenius V, Gustafsson LE, Widstrom O. Tumour necrosis factor-aand nitric oxide, determined as nitrite, in malignant pleural effusion. Respir Med 1994; 88:743-748.
25. Light, RW (1977) Pleural effusions. Med Clin North Am 61,1339-1352.
26. Shimokata K, Saka H, Murate T, et al. Cytokine content in pleural effusions: comprasion betwen tuberculous and carcinomatous pleurisy. Chest 1991; 99:1103-1107.
27. Silva-Mejias C, Gamboa-Antinolo F, Lopes-Cortes LF, et al. Interleukin-ip in pleural fluids of different etiologies. It is role as inflammatory mediator in empyema. Chest 1995; 108:942-945.
28. Aleman C, Alegre J, Monasterio J, et al. Association between inflammatory mediators and fibrinolsis system in infectious pleural effusions. Clin Science 2003; 105:601-607.
29. Monton C, Torres A. Lung inflammatory response in pneumonia. Monaldi Arch Chest Dis 1998; 53:56-63.
30. Ortqvist A, Hedlund J, Wretlind B, ej: al. Diagnostic and prognostic value of interleukin-6 and C-reactive protein in community-acquired pneumonia. Scand J Infect Dis 1995; 27:457-462.
31. Glynn P, Coakley R, Kilgallen I, et al. Circulating interleukin-6 and interleukin 10 in community acquired pneumonia Thorax 1999; 54:51-55.
32. Meduri GU, headley S, Kohler G, et al. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS:plasma IL-ip and IL-6 levels are consistent and efficient predictors of outcome overtime. Chest 1993; 104:399-404.
33. Hirano T, Teranishi T, Lin B, et al. Human hepler T cell factor (s): IV. Demonstration of human late-acting B cell differentiation factor acting ob Staphyllococcus aureus Cowanl-stimulated B cells. J Immunol 1984; 133:798-802.
34. Barnes PF, Mistry SD, Cooper CL, et al. Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis. J Immunol 1989; 142:1114-1119.
35. Soderblom T, Nyberg P, Teppo AM, et al. Pleural fluid interferon- and tumour necrosis factor- in tuberculous and rheumatoid pleurisy. Eur Respir J 1996; 9:1652-1655.
36. Kim YC, Park KO, Bom HS, et al. Combining ADA, protein and IFN- best allows discrimination between tuberculous and malignant pleural effusion. Korean J Intern Med 1997; 12:225-231.