K Law, M Weiden, T Harkin, K Tchou-Wong, C Chi and WN Rom
Department of Medicine, New York University Medical Center, New York 10016, USA.

Mycobacterium tuberculosis and its components have been shown to stimulate mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF- alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involved and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involved sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients that was 5- to 20-fold greater than uninvolved sites, normal controls, or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patients with TB compared with two negative controls. We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection.

This article has been cited by other articles:

				B. Wu, C. Huang, L. Garcia, A. P. de Leon, J. S. Osornio, M. Bobadilla-del-Valle, L. Ferreira, S. Canizales, P. Small, M. Kato-Maeda, et al. Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guerin Infect. Immun., July 1, 2007; 75(7): 3658 - 3664. [Abstract] [Full Text] [PDF]

				D. Sud, C. Bigbee, J. L. Flynn, and D. E. Kirschner Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection J. Immunol., April 1, 2006; 176(7): 4296 - 4314. [Abstract] [Full Text] [PDF]

				C. Carranza, E. Juarez, M. Torres, J. J. Ellner, E. Sada, and S. K. Schwander Mycobacterium tuberculosis Growth Control by Lung Macrophages and CD8 Cells from Patient Contacts Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 238 - 245. [Abstract] [Full Text] [PDF]

				E Unsal, S Aksaray, D Koksal, and T Sipit Potential role of interleukin 6 in reactive thrombocytosis and acute phase response in pulmonary tuberculosis Postgrad. Med. J., September 1, 2005; 81(959): 604 - 607. [Abstract] [Full Text] [PDF]

				M. I. Wickremasinghe, L. H. Thomas, C. M. O'Kane, J. Uddin, and J. S. Friedland Transcriptional Mechanisms Regulating Alveolar Epithelial Cell-specific CCL5 Secretion in Pulmonary Tuberculosis J. Biol. Chem., June 25, 2004; 279(26): 27199 - 27210. [Abstract] [Full Text] [PDF]

				J. A. Gold, Y. Hoshino, N. Tanaka, W. N. Rom, B. Raju, R. Condos, and M. D. Weiden Surfactant Protein A Modulates the Inflammatory Response in Macrophages during Tuberculosis Infect. Immun., February 1, 2004; 72(2): 645 - 650. [Abstract] [Full Text] [PDF]

				S. Munoz, R. Hernandez-Pando, S. N. Abraham, and J. A. Enciso Mast Cell Activation by Mycobacterium tuberculosis: Mediator Release and Role of CD48 J. Immunol., June 1, 2003; 170(11): 5590 - 5596. [Abstract] [Full Text] [PDF]

				M. Kawahara, T. Nakasone, and M. Honda Dynamics of Gamma Interferon, Interleukin-12 (IL-12), IL-10, and Transforming Growth Factor {beta} mRNA Expression in Primary Mycobacterium bovis BCG Infection in Guinea Pigs Measured by a Real-Time Fluorogenic Reverse Transcription-PCR Assay Infect. Immun., December 1, 2002; 70(12): 6614 - 6620. [Abstract] [Full Text] [PDF]

				T. M. O'Connor, F. Shanahan, and C. P. Bredin Infliximab Therapy for Complicated Sarcoidosis Ann Intern Med, August 20, 2002; 137(4): 296 - 297. [Full Text] [PDF]

				R. van Crevel, T. H. M. Ottenhoff, and J. W. M. van der Meer Innate Immunity to Mycobacterium tuberculosis Clin. Microbiol. Rev., April 1, 2002; 15(2): 294 - 309. [Abstract] [Full Text] [PDF]

				J. J. Saukkonen, B. Bazydlo, M. Thomas, R. M. Strieter, J. Keane, and H. Kornfeld {beta}-Chemokines Are Induced by Mycobacterium tuberculosis and Inhibit Its Growth Infect. Immun., April 1, 2002; 70(4): 1684 - 1693. [Abstract] [Full Text] [PDF]

				A. Jeevan, T. Yoshimura, G. Foster, and D. N. McMurray Effect of Mycobacterium bovis BCG Vaccination on Interleukin-1{beta} and RANTES mRNA Expression in Guinea Pig Cells Exposed to Attenuated and Virulent Mycobacteria Infect. Immun., March 1, 2002; 70(3): 1245 - 1253. [Abstract] [Full Text] [PDF]

				J.-i. Ashitani, H. Mukae, T. Hiratsuka, M. Nakazato, K. Kumamoto, and S. Matsukura Elevated Levels of {alpha}-Defensins in Plasma and BAL Fluid of Patients With Active Pulmonary Tuberculosis Chest, February 1, 2002; 121(2): 519 - 526. [Abstract] [Full Text] [PDF]

				B. Raju, C. F. Tung, D. Cheng, N. Yousefzadeh, R. Condos, W. N. Rom, and D. B. Tse In Situ Activation of Helper T Cells in the Lung Infect. Immun., August 1, 2001; 69(8): 4790 - 4798. [Abstract] [Full Text] [PDF]

				J. E. Wigginton and D. Kirschner A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis J. Immunol., February 1, 2001; 166(3): 1951 - 1967. [Abstract] [Full Text] [PDF]

				H.-P. KUO, C.-H. WANG, K.-S. HUANG, H.-C. LIN, C.-T. YU, C.-Y. LIU, and L.-C. LU Nitric Oxide Modulates Interleukin-1beta and Tumor Necrosis Factor-alpha Synthesis by Alveolar Macrophages in Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 192 - 199. [Abstract] [Full Text]

				M. I. Wickremasinghe, L. H. Thomas, and J. S. Friedland Pulmonary Epithelial Cells are a Source of IL-8 in the Response to Mycobacterium tuberculosis: Essential Role of IL-1 from Infected Monocytes in a NF-{kappa}B-Dependent Network J. Immunol., October 1, 1999; 163(7): 3936 - 3947. [Abstract] [Full Text] [PDF]

				M. CASARINI, F. AMEGLIO, L. ALEMANNO, P. ZANGRILLI, P. MATTIA, G. PAONE, A. BISETTI, and S. GIOSUÈ Cytokine Levels Correlate with a Radiologic Score in Active Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 143 - 148. [Abstract] [Full Text]

				S. GIOSUE, M. CASARINI, L. ALEMANNO, G. GALLUCCIO, P. MATTIA, G. PEDICELLI, L. REBEK, A. BISETTI, and F. AMEGLIO Effects of Aerosolized Interferon-alpha in Patients with Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., October 1, 1998; 158(4): 1156 - 1162. [Abstract] [Full Text] [PDF]

				N. P. JUFFERMANS, A. VERBON, S. J. H. van DEVENTER, H. van DEUTEKOM, P. SPEELMAN, and T. van der POLL Tumor Necrosis Factor and Interleukin-1 Inhibitors as Markers of Disease Activity of Tuberculosis Am. J. Respir. Crit. Care Med., April 1, 1998; 157(4): 1328 - 1331. [Abstract] [Full Text] [PDF]

				N. W. SCHLUGER and W. N. ROM The Host Immune Response to Tuberculosis Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): 679 - 691. [Full Text] [PDF]