JJ Bowden, TR Schoeb, JR Lindsey and DM McDonald
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.

Mycoplasma pulmonis infection in rats causes a chronic inflammatory airway disease. Along with extensive remodeling of the airway mucosa, lymphocytic infiltrates, angiogenesis, and mucosal thickening, there is an abnormal sensitivity of the blood vessels to mediators that evoke "neurogenic inflammation". As a result, substance P, a peptide released from sensory nerves, produces an unusually large amount of plasma leakage. These changes can be prevented or reduced by prophylactic treatment with antibiotics, but it is unknown whether the extensive remodeling of the airway mucosa and potentiation of neurogenic inflammation can be reversed once they are established. We addressed this issue in F344 rats that were infected with M. pulmonis at 8 wk of age. Six weeks later, the rats were treated daily with an antibiotic (oxytetracycline, 20 mg/kg intramuscularly), to reduce the number of infecting organisms, or with an antiinflammatory steroid (dexamethasone, 0.5 mg/kg intraperitoneally), to reduce the inflammatory and immunologic response to the infection. Sham-treated infected rats received daily injections of 0.9% NaCl. After 1, 2, or 4 wk of treatment the rats were anesthetized and then challenged with substance P (5 micrograms/kg intravenously). The sham-treated rats had pathologic changes in their airways typical of severe M. pulmonis infection, and had as much as a threefold increase in substance P- induced plasma leakage. By comparison, after 4 wk of treatment with oxytetracycline or dexamethasone, the chronic inflammation was nearly resolved and the response to substance P was in the normal range. Unexpectedly, dexamethasone, like oxytetracycline, reduced the number of infecting organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				N. Nisar, R. Guleria, S. Kumar, T. Chand Chawla, and N. Ranjan Biswas Mycoplasma pneumoniae and its role in asthma Postgrad. Med. J., February 1, 2007; 83(976): 100 - 104. [Abstract] [Full Text] [PDF]

				D. M. McDonald and P. Baluk Imaging of Angiogenesis in Inflamed Airways and Tumors: Newly Formed Blood Vessels Are Not Alike and May Be Wildly Abnormal: Parker B. Francis Lecture Chest, December 1, 2005; 128(6_suppl): 602S - 608S. [Full Text] [PDF]

				A. B. Aurora, P. Baluk, D. Zhang, S. S. Sidhu, G. M. Dolganov, C. Basbaum, D. M. McDonald, and N. Killeen Immune Complex-Dependent Remodeling of the Airway Vasculature in Response to a Chronic Bacterial Infection J. Immunol., November 15, 2005; 175(10): 6319 - 6326. [Abstract] [Full Text] [PDF]

				H. A. Boushey New and Exploratory Therapies for Asthma Chest, March 1, 2003; 123(2007): 439S - 445S. [Full Text] [PDF]

				R. D. Hardy, H. S. Jafri, K. Olsen, J. Hatfield, J. Iglehart, B. B. Rogers, P. Patel, G. Cassell, G. H. McCracken, and O. Ramilo Mycoplasma pneumoniae Induces Chronic Respiratory Infection, Airway Hyperreactivity, and Pulmonary Inflammation: a Murine Model of Infection-Associated Chronic Reactive Airway Disease Infect. Immun., February 1, 2002; 70(2): 649 - 654. [Abstract] [Full Text] [PDF]

				D. M. MCDONALD Angiogenesis and Remodeling of Airway Vasculature in Chronic Inflammation Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): S39 - 45. [Abstract] [Full Text] [PDF]

				H. W. Chu, M. Kraft, M. D. Rex, and R. J. Martin Evaluation of Blood Vessels and Edema in the Airways of Asthma Patients : Regulation With Clarithromycin Treatment Chest, August 1, 2001; 120(2): 416 - 422. [Abstract] [Full Text] [PDF]

				T. Ezaki, P. Baluk, G. Thurston, A. La Barbara, C. Woo, and D. M. McDonald Time Course of Endothelial Cell Proliferation and Microvascular Remodeling in Chronic Inflammation Am. J. Pathol., June 1, 2001; 158(6): 2043 - 2055. [Abstract] [Full Text] [PDF]

				R. J. Martin, H. W. Chu, J. M. Honour, and R. J. Harbeck Airway Inflammation and Bronchial Hyperresponsiveness after Mycoplasma pneumoniae Infection in a Murine Model Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 577 - 582. [Abstract] [Full Text]

				T. Casale Immunobiology of Asthma and Rhinitis . Pathogenic Factors and Therapeutic Options Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1778 - 1787. [Full Text]

				S. R. Akhter, H. Ikezaki, X.-P. Gao, and I. Rubinstein Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo J Appl Physiol, May 1, 1999; 86(5): 1603 - 1609. [Abstract] [Full Text] [PDF]

				A. Dahlqvist, E. Y. Umemoto, J. J. Brokaw, M. Dupuis, and D. M. McDonald Tissue Macrophages Associated with Angiogenesis in Chronic Airway Inflammation in Rats Am. J. Respir. Cell Mol. Biol., February 1, 1999; 20(2): 237 - 247. [Abstract] [Full Text]

				L. H. K. Lim, B. S. Bochner, and E. M. Wagner Leukocyte recruitment in the airways: an intravital microscopic study of rat tracheal microcirculation Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L959 - L967. [Abstract] [Full Text] [PDF]