DC Deetz, PJ Jagielo, TJ Quinn, PS Thorne, SA Bleuer and DA Schwartz
Department of Internal Medicine, The University of Iowa College of Medicine, Iowa City 52242-1081, USA.

To characterize the kinetics of grain dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole- lung lavage in mice following a single inhalation exposure to comparable dosages of corn dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL- 6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of grain dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of grain dust-induced inflammation.

This article has been cited by other articles:

				S. Hadina, J. P. Weiss, P. B. McCray Jr., K. Kulhankova, and P. S. Thorne MD-2-Dependent Pulmonary Immune Responses to Inhaled Lipooligosaccharides: Effect of Acylation State Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 647 - 654. [Abstract] [Full Text] [PDF]

				M. S. Bolger, D. S. Ross, H. Jiang, M. M. Frank, A. J. Ghio, D. A. Schwartz, and J. R. Wright Complement levels and activity in the normal and LPS-injured lung Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L748 - L759. [Abstract] [Full Text] [PDF]

				P. S. Thorne, K. Kulhankova, M. Yin, R. Cohn, S. J. Arbes Jr., and D. C. Zeldin Endotoxin Exposure Is a Risk Factor for Asthma: The National Survey of Endotoxin in United States Housing Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1371 - 1377. [Abstract] [Full Text] [PDF]

				E. Abraham Effects of Recombinant Human Activated Protein C in Human Models of Endotoxin Administration Proceedings of the ATS, October 1, 2005; 2(3): 243 - 247. [Abstract] [Full Text] [PDF]

				J. W. Hollingsworth, B. J. Chen, D. M. Brass, K. Berman, M. D. Gunn, D. N. Cook, and D. A. Schwartz The Critical Role of Hematopoietic Cells in Lipopolysaccharide-induced Airway Inflammation Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 806 - 813. [Abstract] [Full Text] [PDF]

				T. D. LeVan, S. Von Essen, D. J. Romberger, G. P. Lambert, F. D. Martinez, M. M. Vasquez, and J. A. Merchant Polymorphisms in the CD14 Gene Associated with Pulmonary Function in Farmers Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 773 - 779. [Abstract] [Full Text] [PDF]

				D. A. Schwartz, J. H. Freedman, and E. A. Linney Environmental genomics: a key to understanding biology, pathophysiology and disease Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R217 - R224. [Abstract] [Full Text] [PDF]

				C. L. S. George, M. L. White, M. E. O'Neill, P. S. Thorne, D. A. Schwartz, and J. M. Snyder Altered surfactant protein A gene expression and protein metabolism associated with repeat exposure to inhaled endotoxin Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1337 - L1344. [Abstract] [Full Text] [PDF]

				K. A. Pacheco, C. McCammon, A. H. Liu, P. S. Thorne, M. E. O'Neill, J. Martyny, L. S. Newman, R. F. Hamman, and C. S. Rose Airborne Endotoxin Predicts Symptoms in Non-Mouse-sensitized Technicians and Research Scientists Exposed to Laboratory Mice Am. J. Respir. Crit. Care Med., April 1, 2003; 167(7): 983 - 990. [Abstract] [Full Text] [PDF]

				J. D. Savov, S. H. Gavett, D. M. Brass, D. L. Costa, and D. A. Schwartz Neutrophils play a critical role in development of LPS-induced airway disease Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L952 - L962. [Abstract] [Full Text] [PDF]

				J. G. Moreland, R. M. Fuhrman, J. A. Pruessner, and D. A. Schwartz CD11b and Intercellular Adhesion Molecule-1 Are Involved in Pulmonary Neutrophil Recruitment in Lipopolysaccharide-Induced Airway Disease Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 474 - 480. [Abstract] [Full Text] [PDF]

				E. Lorenz, J. P. Mira, K. L. Frees, and D. A. Schwartz Relevance of Mutations in the TLR4 Receptor in Patients With Gram-Negative Septic Shock Arch Intern Med, May 13, 2002; 162(9): 1028 - 1032. [Abstract] [Full Text] [PDF]

				E. Lorenz, M. Jones, C. Wohlford-Lenane, N. Meyer, K. L. Frees, N. C. Arbour, and D. A. Schwartz Genes other than TLR4 are involved in the response to inhaled LPS Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1106 - L1114. [Abstract] [Full Text] [PDF]

				C. Fiuza and A. F. Suffredini Human models of innate immunity: local and systemic inflammatory responses Innate Immunity, October 1, 2001; 7(5): 385 - 388. [Abstract] [PDF]

				D. A. Schwartz The role of TLR4 in endotoxin responsiveness in humans Innate Immunity, October 1, 2001; 7(5): 389 - 393. [Abstract] [PDF]

				E. N. Schachter, E. Zuskin, N. Rienzi, S. Goswami, V. Castranova, M. Whitmer, and P. Siegel Pharmacologic Properties of Brewery Dust Extracts In Vitro Chest, June 1, 2001; 119(6): 1870 - 1877. [Abstract] [Full Text] [PDF]

				N. P. O'GRADY, H. L. PREAS II, J. PUGIN, C. FIUZA, M. TROPEA, D. REDA, S. M. BANKS, and A. F. SUFFREDINI Local Inflammatory Responses following Bronchial Endotoxin Instillation in Humans Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1591 - 1598. [Abstract] [Full Text] [PDF]

				D. A. Schwartz, W. J. Christ, S. R. Kleeberger, and C. L. Wohlford-Lenane Inhibition of LPS-induced airway hyperresponsiveness and airway inflammation by LPS antagonists Am J Physiol Lung Cell Mol Physiol, April 1, 2001; 280(4): L771 - L778. [Abstract] [Full Text] [PDF]

				C. L. S. George, H. Jin, C. L. Wohlford-Lenane, M. E. O'Neill, J. C. Phipps, P. O'Shaughnessy, J. N. Kline, P. S. Thorne, and D. A. Schwartz Endotoxin responsiveness and subchronic grain dust-induced airway disease Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L203 - L213. [Abstract] [Full Text] [PDF]

				J. G. Moreland, R. M. Fuhrman, C. L. Wohlford-Lenane, T. J. Quinn, E. Benda, J. A. Pruessner, and D. A. Schwartz TNF-{alpha} and IL-1{beta} are not essential to the inflammatory response in LPS-induced airway disease Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L173 - L180. [Abstract] [Full Text] [PDF]

				Y.-C. Kuo, N.-S. Yang, C.-J. Chou, L.-C. Lin, and W.-J. Tsai Regulation of Cell Proliferation, Gene Expression, Production of Cytokines, and Cell Cycle Progression in Primary Human T Lymphocytes by Piperlactam S Isolated from Piper kadsura Mol. Pharmacol., November 1, 2000; 58(5): 1057 - 1066. [Abstract] [Full Text]

				E. MONSO, R. MAGAROLAS, K. RADON, B. DANUSER, M. IVERSEN, C. WEBER, U. OPRAVIL, K. J. DONHAM, and D. NOWAK Respiratory Symptoms of Obstructive Lung Disease in European Crop Farmers Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1246 - 1250. [Abstract] [Full Text] [PDF]

				J. N. Kline, P. J. Jagielo, J. L. Watt, and D. A. Schwartz Bronchial hyperreactivity is associated with enhanced grain dust-induced airflow obstruction J Appl Physiol, September 1, 2000; 89(3): 1172 - 1178. [Abstract] [Full Text] [PDF]

				T. J. Quinn, S. Taylor, C. L. Wohlford-Lenane, and D. A. Schwartz IL-10 reduces grain dust-induced airway inflammation and airway hyperreactivity J Appl Physiol, January 1, 2000; 88(1): 173 - 179. [Abstract] [Full Text] [PDF]

				P. D. Blanc Husker Days and Fever Nights : Counting Cases of Organic Dust Toxic Syndrome Chest, November 1, 1999; 116(5): 1157 - 1158. [Full Text] [PDF]

				S. BECKER, W. A. CLAPP, J. QUAY, K. L. FREES, H. S. KOREN, and D. A. SCHWARTZ Compartmentalization of the Inflammatory Response to Inhaled Grain Dust Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1309 - 1318. [Abstract] [Full Text]

				J. N. KLINE, J. D. COWDEN, G. W. HUNNINGHAKE, B. C. SCHUTTE, J. L. WATT, C. L. WOHLFORD-LENANE, L. S. POWERS, M. P. JONES, and D. A. SCHWARTZ Variable Airway Responsiveness to Inhaled Lipopolysaccharide Am. J. Respir. Crit. Care Med., July 1, 1999; 160(1): 297 - 303. [Abstract] [Full Text]

				P. S. Thorne, P. B. McCray Jr., T. S. Howe, and M. A. O'Neill Early-Onset Inflammatory Responses In Vivo to Adenoviral Vectors in the Presence or Absence of Lipopolysaccharide-Induced Inflammation Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1155 - 1164. [Abstract] [Full Text]

				C. L. Wohlford-Lenane, D. C. Deetz, and D. A. Schwartz. Cytokine gene expression after inhalation of corn dust Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L736 - L743. [Abstract] [Full Text] [PDF]

				P. Lacy, F. Levi-Schaffer, S. Mahmudi-Azer, B. Bablitz, S. C. Hagen, J. Velazquez, A. B. Kay, and R. Moqbel Intracellular Localization of Interleukin-6 in Eosinophils From Atopic Asthmatics and Effects of Interferon gamma   Blood, April 1, 1998; 91(7): 2508 - 2516. [Abstract] [Full Text] [PDF]

				N. N. JARJOUR, S. P. PETERS, R. DJUKANOVIC, and W. J. CALHOUN Investigative Use of Bronchoscopy in Asthma Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): 692 - 697. [Full Text] [PDF]

				P. J. Jagielo, T. J. Quinn, N. Qureshi, and D. A. Schwartz Grain dust-induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L26 - L31. [Abstract] [Full Text] [PDF]