Dexamethasone and oxytetracycline reverse the potentiation of neurogenic inflammation in airways of rats with Mycoplasma pulmonis infection

Jeffrey J. Bowden, Trenton R. Schoeb, J. Russell Lindsey, Donald M. Mcdonald

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 μg/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. We conclude that the potentiation of neurogenic inflammation and many of the other changes associated with the chronic airway disease produced by M. pulmonis infection can be reversed by antibiotics or antiinflammatory steroids.

Original languageEnglish
Pages (from-to)1391-1401
Number of pages11
JournalAmerican journal of respiratory and critical care medicine
Volume150
Issue number5
DOIs
Publication statusPublished - Nov 1994

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