A Magnan, JL Mege, JC Escallier, J Brisse, C Capo, M Reynaud, P Thomas, B Meric, L Garbe, M Badier, L Viard, P Bongrand, R Giudicelli, D Metras, P Fuentes, D Vervloet and M Noirclerc
Chest Medicine and Allergy Department, U INSERM 387, St.-Marguerite Hospital, Marseilles, France.

Acute inflammation in the lung is characterized by a phase of tissue injury followed by a phase of tissue repair. When the latter is excessive, fibrosis occurs. Alveolar macrophages (AM) can produce cytokines involved in both phases of acute lung inflammation, notably interleukin-6 (IL-6), involved in injury and transforming growth factor- beta (TGF-beta), mediating repair. We hypothesized that AM were activated in both phases, and studied IL-6 and TGF-beta production by AM during complications of lung transplantation, acute rejection (AR), and cytomegalovirus pneumonitis (CMVP). In addition, we analyzed these cytokines in bronchiolitis obliterans (BO), a fibrotic complication of lung transplantation linked to previous AR and CMVP. At the onset of AR and CMVP, IL-6 secretion increased, whereas AM TGF-beta content was increased, but not its secretion. In contrast, with time, IL-6 reached control value whereas TGF-beta secretion rose significantly. In BO, IL- 6 was not oversecreted, but TGF-beta increased, notably before functional abnormalities occurred. These results show that during acute complications of lung transplantation, AM display an early activation with oversecretion of IL-6, which is involved in tissue injury, counterbalanced by a late activation in which TGF-beta predominates, mediating tissue repair. The results provide new insights into the pathogenesis of BO, which is linked to acute complications of lung transplantation through this biphasic AM activation.

This article has been cited by other articles:

				Y. Y. Koh, D. E. Jung, J. Y. Koh, J. Y. Kim, Y. Yoo, and C. K. Kim Bronchoalveolar Cellularity and Interleukin-8 Levels in Measles Bronchiolitis Obliterans Chest, May 1, 2007; 131(5): 1454 - 1460. [Abstract] [Full Text] [PDF]

				J. D. Lande, J. Patil, N. Li, T. R. Berryman, R. A. King, and M. I. Hertz Novel Insights into Lung Transplant Rejection by Microarray Analysis Proceedings of the ATS, January 1, 2007; 4(1): 44 - 51. [Abstract] [Full Text] [PDF]

				B. S. Lu, A. D. Yu, X. Zhu, E. R. Garrity Jr, W. T. Vigneswaran, and S. M. Bhorade Sequential gene expression profiling in lung transplant recipients with chronic rejection. Chest, September 1, 2006; 130(3): 847 - 854. [Abstract] [Full Text] [PDF]

				D. S. Wilkes, T. M. Egan, and H. Y. Reynolds Lung Transplantation: Opportunities for Research and Clinical Advancement Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 944 - 955. [Abstract] [Full Text] [PDF]

				J. J. Fullmer, L. L. Fan, M. K. Dishop, C. Rodgers, and R. Krance Successful Treatment of Bronchiolitis Obliterans in a Bone Marrow Transplant Patient With Tumor Necrosis Factor-{alpha} Blockade Pediatrics, September 1, 2005; 116(3): 767 - 770. [Abstract] [Full Text] [PDF]

				U. Bartram and C. P. Speer The Role of Transforming Growth Factor {beta} in Lung Development and Disease Chest, February 1, 2004; 125(2): 754 - 765. [Abstract] [Full Text] [PDF]

				A. Boehler and M. Estenne Post-transplant bronchiolitis obliterans Eur. Respir. J., December 1, 2003; 22(6): 1007 - 1018. [Abstract] [Full Text] [PDF]

				V. J. Gimino, J. D. Lande, T. R. Berryman, R. A. King, and M. I. Hertz Gene Expression Profiling of Bronchoalveolar Lavage Cells in Acute Lung Rejection Am. J. Respir. Crit. Care Med., November 15, 2003; 168(10): 1237 - 1242. [Abstract] [Full Text] [PDF]

				D. Mokart, B. P. Guery, R. Bouabdallah, C. Martin, J.-L. Blache, C. Arnoulet, and J.-L. Mege Deactivation of Alveolar Macrophages in Septic Neutropenic ARDS Chest, August 1, 2003; 124(2): 644 - 652. [Abstract] [Full Text] [PDF]

				M. Estenne and M. I. Hertz Bronchiolitis Obliterans after Human Lung Transplantation Am. J. Respir. Crit. Care Med., August 15, 2002; 166(4): 440 - 444. [Full Text] [PDF]

				R. M. Aris, S. Walsh, W. Chalermskulrat, V. Hathwar, and I. P. Neuringer Growth Factor Upregulation during Obliterative Bronchiolitis in the Mouse Model Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 417 - 422. [Abstract] [Full Text] [PDF]

				D.-J. SLEBOS, J. SCHOLMA, H. MARIKE BOEZEN, G. H. KOETER, W. VAN DER BIJ, D. S. POSTMA, and H. F. KAUFFMAN Longitudinal Profile of Bronchoalveolar Lavage Cell Characteristics in Patients with a Good Outcome after Lung Transplantation Am. J. Respir. Crit. Care Med., February 15, 2002; 165(4): 501 - 507. [Abstract] [Full Text] [PDF]

				J. SCHOLMA, D.-J. SLEBOS, H. MARIKE BOEZEN, J. W. K. van den BERG, W. van der BIJ, W. J. de BOER, G. H. KOËTER, W. TIMENS, H. F. KAUFFMAN, and D. S. POSTMA Eosinophilic Granulocytes and Interleukin-6 Level in Bronchoalveolar Lavage Fluid Are Associated with the Development of Obliterative Bronchiolitis after Lung Transplantation Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2221 - 2225. [Abstract] [Full Text]

				J. HIRSCH, A. ELSSNER, G. MAZUR, K. L. MAIER, I. BITTMANN, J. BEHR, M. SCHWAIBLMAIR, H. REICHENSPURNER, H. FÜRST, J. BRIEGEL, et al. Bronchiolitis Obliterans Syndrome after (Heart-)Lung Transplantation . Impaired Antiprotease Defense and Increased Oxidant Activity Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1640 - 1646. [Abstract] [Full Text]

				H. W. CHU, J. L. HALLIDAY, R. J. MARTIN, D. Y. M. LEUNG, S. J. SZEFLER, and S. E. WENZEL Collagen Deposition in Large Airways May Not Differentiate Severe Asthma from Milder Forms of the Disease Am. J. Respir. Crit. Care Med., December 1, 1998; 158(6): 1936 - 1944. [Abstract] [Full Text] [PDF]