RB Goodman, RM Strieter, DP Martin, KP Steinberg, JA Milberg, RJ Maunder, SL Kunkel, A Walz, LD Hudson and TR Martin
Medical Research Service, Seattle VA Medical Center, Washington, USA.

To determine the relationship between airspace cytokines and cellular inflammatory responses in patients with the acute respiratory distress syndrome (ARDS), we performed bronchoalveolar lavage (BAL) in 82 prospectively identified, mechanically ventilated patients on Days 3, 7, 14, and/or 21 after the onset of ARDS. We studied the relationships between bronchoalveolar lavage fluid (BALF) cell populations and the concentrations of two potent neutrophil (PMN) chemoattractants, interleukin-8 (IL-8) and epithelial cell-derived neutrophil activator- 78 (ENA-78); two potent monocyte chemoattractants, monocyte chemotactic peptide-1 (MCP-1) and macrophage inflammatory peptide-1 alpha (MIP-1 alpha); and the early response cytokine interleukin-1 beta (IL-1 beta) and its naturally occurring antagonist, IL-1 receptor antagonist protein (IRAP). We found that all of these cytokines were significantly increased regardless of the duration of ARDS. IL-8 and ENA-78 were the cytokines most strongly and consistently correlated with PMN concentrations in the lung fluids of patients with ARDS, and the correlations were independent of the other cytokines or coexisting lung infection. None of the cytokines tested correlated with macrophage concentrations. MCP-1 was directly correlated with lung injury score on Days 7, 14, and 21. Although neither IL-8 nor ENA-78 was associated with outcome, levels of IL-1 beta measured on Day 7 were associated with an increased risk of death (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.1 to 7.4). These data demonstrate potential molecular mechanisms of the persistent inflammatory process in the lungs of patients with ARDS.

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				T. Geiser, P.-H. Jarreau, K. Atabai, and M. A. Matthay Interleukin-1beta augments in vitro alveolar epithelial repair Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1184 - L1190. [Abstract] [Full Text] [PDF]

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				E. Abraham, J. Arcaroli, A. Carmody, H. Wang, and K. J. Tracey Cutting Edge: HMG-1 as a Mediator of Acute Lung Inflammation J. Immunol., September 15, 2000; 165(6): 2950 - 2954. [Abstract] [Full Text] [PDF]

				L. A. Miller, J. Usachenko, R. J. McDonald, and D. M. Hyde Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms J. Leukoc. Biol., August 1, 2000; 68(2): 201 - 208. [Abstract] [Full Text]

				T. R. Martin Recognition of Bacterial Endotoxin in the Lungs Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 128 - 132. [Full Text]

				S. Rosseau, P. Hammerl, U. Maus, H.-D. Walmrath, H. Schutte, F. Grimminger, W. Seeger, and J. Lohmeyer Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L25 - L35. [Abstract] [Full Text] [PDF]

				M. NAKAMURA, S. FUJISHIMA, M. SAWAFUJI, A. ISHIZAKA, T. OGUMA, K. SOEJIMA, H. MATSUBARA, S. TASAKA, K. KIKUCHI, K. KOBAYASHI, et al. Importance of Interleukin-8 in the Development of Reexpansion Lung Injury in Rabbits Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 1030 - 1036. [Abstract] [Full Text] [PDF]

				G. L. Allen, I. Y. Menendez, M. A. Ryan, R. L. Mazor, J. R. Wispe, M. A. Fiedler, and H. R. Wong Hyperoxia synergistically increases TNF-alpha -induced interleukin-8 gene expression in A549 cells Am J Physiol Lung Cell Mol Physiol, February 1, 2000; 278(2): L253 - L260. [Abstract] [Full Text] [PDF]

				T. T Bauer, C. Montón, A. Torres, H. Cabello, X. Fillela, A. Maldonado, J.-M. Nicolás, and E. Zavala Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls Thorax, January 1, 2000; 55(1): 46 - 52. [Abstract] [Full Text]

				S. Rosseau, J. Selhorst, K. Wiechmann, K. Leissner, U. Maus, K. Mayer, F. Grimminger, W. Seeger, and J. Lohmeyer Monocyte Migration Through the Alveolar Epithelial Barrier: Adhesion Molecule Mechanisms and Impact of Chemokines J. Immunol., January 1, 2000; 164(1): 427 - 435. [Abstract] [Full Text] [PDF]

				S. Rosseau, P. Hammerl, U. Maus, A. Gunther, W. Seeger, F. Grimminger, and J. Lohmeyer Surfactant Protein A Down-Regulates Proinflammatory Cytokine Production Evoked by Candida albicans in Human Alveolar Macrophages and Monocytes J. Immunol., October 15, 1999; 163(8): 4495 - 4502. [Abstract] [Full Text] [PDF]

				E. R. Goodman, P. Stricker, M. Velavicius, R. Fonseca, E. Kleinstein, R. Lavery, E. A. Deitch, C. J. Hauser, and H. H. Simms Role of Granulocyte-Macrophage Colony-Stimulating Factor and Its Receptor in the Genesis of Acute Respiratory Distress Syndrome Through an Effect on Neutrophil Apoptosis Arch Surg, October 1, 1999; 134(10): 1049 - 1054. [Abstract] [Full Text] [PDF]

				G. Asimakopoulos, P. L.C. Smith, C. P. Ratnatunga, and K. M. Taylor Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass Ann. Thorac. Surg., September 1, 1999; 68(3): 1107 - 1115. [Abstract] [Full Text] [PDF]

				V. M. Ranieri, P. M. Suter, C. Tortorella, R. De Tullio, J. M. Dayer, A. Brienza, F. Bruno, and A. S. Slutsky Effect of Mechanical Ventilation on Inflammatory Mediators in Patients With Acute Respiratory Distress Syndrome: A Randomized Controlled Trial JAMA, July 7, 1999; 282(1): 54 - 61. [Abstract] [Full Text] [PDF]

				T. R. Martin Lung Cytokines and ARDS: Roger S. Mitchell Lecture Chest, July 1, 1999; 116 (2009): 2S - 8S. [Full Text]

				A. L. Picone, C. J. Lutz, C. Finck, D. Carney, L. A. Gatto, A. Paskanik, B. Searles, K. Snyder, and G. Nieman Multiple sequential insults cause post-pump syndrome Ann. Thorac. Surg., April 1, 1999; 67(4): 978 - 985. [Abstract] [Full Text] [PDF]

				M. M. Monick, A. B. Carter, G. Gudmundsson, R. Mallampalli, L. S. Powers, and G. W. Hunninghake A Phosphatidylcholine-Specific Phospholipase C Regulates Activation of p42/44 Mitogen-Activated Protein Kinases in Lipopolysaccharide-Stimulated Human Alveolar Macrophages J. Immunol., March 1, 1999; 162(5): 3005 - 3012. [Abstract] [Full Text] [PDF]

				C. J. Cummings, T. R. Martin, C. W. Frevert, J. M. Quan, V. A. Wong, S. M. Mongovin, T. R. Hagen, K. P. Steinberg, and R. B. Goodman Expression and Function of the Chemokine Receptors CXCR1 and CXCR2 in Sepsis J. Immunol., February 15, 1999; 162(4): 2341 - 2346. [Abstract] [Full Text] [PDF]

				B. Neumann, N. Zantl, A. Veihelmann, K. Emmanuilidis, K. Pfeffer, C.-D. Heidecke, and B. Holzmann Mechanisms of acute inflammatory lung injury induced by abdominal sepsis Int. Immunol., February 1, 1999; 11(2): 217 - 227. [Abstract] [Full Text] [PDF]

				E. R. Goodman, E. Kleinstein, A. M. Fusco, D. P. Quinlan, R. Lavery, D. H. Livingston, E. A. Deitch, and C. J. Hauser Role of Interleukin 8 in the Genesis of Acute Respiratory Distress Syndrome Through an Effect on Neutrophil Apoptosis Arch Surg, November 1, 1998; 133(11): 1234 - 1239. [Abstract] [Full Text] [PDF]

				R. B. Goodman, R. M. Strieter, C. W. Frevert, C. J. Cummings, P. Tekamp-Olson, S. L. Kunkel, A. Walz, and T. R. Martin Quantitative comparison of C-X-C chemokines produced by endotoxin-stimulated human alveolar macrophages Am J Physiol Lung Cell Mol Physiol, July 1, 1998; 275(1): L87 - L95. [Abstract] [Full Text] [PDF]

				P. Aukrust, T. Ueland, F. Muller, A. K. Andreassen, I. Nordoy, H. Aas, J. Kjekshus, S. Simonsen, S. S. Froland, and L. Gullestad Elevated Circulating Levels of C-C Chemokines in Patients With Congestive Heart Failure Circulation, March 31, 1998; 97(12): 1136 - 1143. [Abstract] [Full Text] [PDF]

				A. B. Carter, M. M. Monick, and G. W. Hunninghake Lipopolysaccharide-induced NF-kappa B Activation and Cytokine Release in Human Alveolar Macrophages Is PKC-independent and TK- and PC-PLC-dependent Am. J. Respir. Cell Mol. Biol., March 1, 1998; 18(3): 384 - 391. [Abstract] [Full Text]

				Q. Zhao, L. G. Simpson, K. E. Driscoll, and G. D. Leikauf Chemokine regulation of ozone-induced neutrophil and monocyte inflammation Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L39 - L46. [Abstract] [Full Text] [PDF]

				G Matute-Bello, W. Liles, F Radella 2nd, K. Steinberg, J. Ruzinski, M Jonas, E. Chi, L. Hudson, and T. Martin Neutrophil apoptosis in the acute respiratory distress syndrome Am. J. Respir. Crit. Care Med., December 1, 1997; 156(6): 1969 - 1977. [Abstract] [Full Text]

				T.-a. Imaizumi, K. H. Albertine, D. L. Jicha, T. M. McIntyre, S. M. Prescott, and G. A. Zimmerman Human Endothelial Cells Synthesize ENA-78: Relationship to IL-8 and to Signaling of PMN Adhesion Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 181 - 192. [Abstract] [Full Text]