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Title Expression of CTGF and TNFa in alveolar macrophages of patients with idiopathic pulmonary fibrosis before and after treatment with azathioprine or interferon-γ-1b
Author Areti Xifteri, Fotis Drakopanagiotakis, Argyris Tzouvelekis, Evangelos Tsiambas, Andreas Karameris, Katerina Tsakanika, Vlassis Polychronopoulos, Demosthenes Bouros
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal lung disorder the aetiology of which is unknown and for which there is no effective therapy. Connective tissue growth factor (CTGF) and tumour necrosis factor alpha (TNFα) have been reported to participate significantly in the pathogenesis of the disease. The role of alveolar macrophages in the expression of these cytokines remains unclear. Materials and Methods: Samples of bronchoalveolar lavage fluid (BALF) derived from 20 newly diagnosed patients with IPF before and after 6 months of treatment with either interferon (IFN-γ-1b) and prednisolone (10 patients) or azathioprine (AZA) and prednisolone (10 patients) and from 10 normal subjects (control group) were used for the analysis of CTGF and TNFα protein expression in the alveolar macrophages. The effectiveness of the two drug regimes on the pulmonary function tests (FEV1, FVC, DLCO) and PaO2 and PaCO2 of the patients with IPF was investigated. Results: Decreased CTGF protein expression was detected in the patients with IPF compared with the control group (p=0.001). TNFα expression in IPF patients did not differ from that of the normal control subjects. Neither of the drug regimes affected the protein expression of these factorsor the pulmonary function parameters. Conclusion: These findings suggest that the alveolar macrophages are not the main source of CTGF and TNFα in IPF. Treatment with either AZA or IFN-γ-1b did not result in any significant change in the protein expression of these factors.
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References
1. ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS.JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011; 183:788-824.

2. Bouros D. Combined pulmonary fibrosis and emphysema syndrome. Pneumon 2009; 22:128-130.

3. American Thoracic Society. ATS/ERS international multidisciplinary consensus classification of idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002; 165:277–304.

4. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001; 345:517–525.

5. Selman M, King TE, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001; 134:136–151.

6. Antoniou KM, Alexandrakis MG, Siafakas NM, Bouros D. Cytokine network in the pathogenesis of idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:91-104.

7. Abraham DJ, Shiwen X, Black CM, et al. Tumor necrosis factor-a suppresses the induction of connective tissue growth factor by transforming growth factor-b in normal and scleroderma fibroblasts. J Biol Chem 2000;275:15220–5.

8. Pan LH, Yamauchi K, Uzuki M, et al. Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF. Eur Respir J 2001;17:1220-7.

9. Kelly M, Kolb M, Bonniaud P, Gauldie J. Re-evaluation of fibrogenic cytokines in lung fibrosis. Curr Pharm Des 2003;9:39-49. 

10. Gharaee-Kermani M, Phan SH. Molecular mechanisms of and possible treatment strategies for idiopathic pulmonary fibrosis. Curr Pharm Des 2005;11:3943-71.

11. Zhang K, Gharaee-Kermani M, McGarry B, Remick D, Phan SH. TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis. J Immunol 1997;158:954-9.

12. Fujita M, Shannon JM, Morikawa O, Gauldie J, Hara N, Mason RJ. Overexpression of tumor necrosis factor-alpha diminishes pulmonary fibrosis induced by bleomycin or transforming growth factor-beta. Am J Respir Cell Mol Biol 2003;29:669-76. 

13. Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am Rev Respir Dis 1991;144:291-296.

14. Antoniou KM, Nicholson AG, Dimadi M, et al. Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis. Eur Respir J 2006;28:496-504.

15. Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 2004; 350:125-133.

16. Malagari K, Siafakas N, Economidou F, et al. Clinical, radiological and molecular effects in three patients with idiopathic pulmonary fibrosis after long-term treatment with interferon gamma-1b. Pneumon 2009;22:162-8.

17. Bouros D. The new ATS/ERS/JRS IPF Guidelines. Pneumon 2008; 21:117-118.
18. Bouros D. Interferon gamma for idiopathic pulmonary fibrosis. Lancet 2009;374:180-2.

19. Karagiannidis N, Tsakanika K, Drakopanagiotakis F, et al. Syndromes, diseases and the challenge of definitions in intensive care medicine: the case of acute respiratory distress syndrome. Pneumon 2009;22:247-253.

20. Keane MP. The role of chemokines and cytokines in lung fibrosis Eur Respir Rev 2008;17:109,151–156.

21. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-tomacrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 2006;177:7303–7311.

22. Tzouvelekis A, Bouros E, Bouros D. The Immunology of pulmonary fibrosis: The role of Th1/Th2/Th17/Treg cells. Pneumon 2010;23:17-20.

23. Kotsianidis I, Bouros D, Nakou E, Tzouvelekis A. Impaired T cell regulation in interstitial lung disease: a new culprit for an old case? Pneumon 2007;20:327-329.

24. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity 2005;23:344–346

25. Shearer JD, Richards JR, Mills CD, Caldwell MD. Differential regulation of macrophage arginine metabolism:a proposed role in wound healing. Am J Physiol 1997;272:E181–E190.

26. Robert M. Strieter What Differentiates Normal Lung Repair and Fibrosis? Inflammation, Resolution of Repair, and Fibrosis Proc Am Thorac Soc 2008;5:305–310.

27. Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Report of the European Society of Pneumology Task Group. Eur Respir J 1989;2:561-585.

28. Clinical guidelines and indications for bronchoalveolar lavage (BAL): Report of the European Society of Pneumology Task Group on BAL. Eur Respir J 1990;3:937-976.

29. Tzortzaki EG, Antoniou KM, Zervou MI, et al. Effects of antifibrotic agents on TGF-beta1, CTGF and IFN-gamma expression in patients with idiopathic pulmonary fibrosis. Respir Med. 2007; 101:1821-9.

30. Martinez JA, King TE Jr, Brown K, et al. Increased expression of the interleukin-10 gene by alveolar macrophages in interstitial lung disease. Am J Physiol. 1997;273:L676-83.

31. Homolka J, Ziegenhagen MW, Gaede KI, Entzian P, Zissel G, Müller-Quernheim J. Systemic immune cell activation in a subgroup of patients with idiopathic pulmonary fibrosis. Respiration. 2003; 70:262-9.

32. Nash JR, McLaughlin PJ, Butcher D, Corrin B. Expression of tumour necrosis factor-alpha in cryptogenic fibrosing alveolitis. Histopathology. 1993; 22:343-7.

33. King TE Jr, Albera C, Bradford WZ, et al; INSPIRE Study Group. 
Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet 2009;374:222-8. 

34. Bouros D, Antoniou KM. Current and future therapeutic approaches in idiopathic pulmonary fibrosis. Eur Respir J 2005;26:693-702.

35. Noble PW, Albera C, Bradford WZ, et al; CAPACITY Study Group. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011;377:1760-9.

36. Bouros D. Pirfenidone for idiopathic pulmonary fibrosis Lancet 2011;377:1727-9.

37. Antoniou KM, Ferdoutsis E, Bouros D. Interferons and their application in the diseases of the lung. Chest 2003;123:209-16.
Keywords Idiopathic pulmonary fibrosis, azathioprine, interferon-γ-1b, bronchoalveolar lavage, CTGF, TNFα, alveolar macrophages
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