DEXAMETHASONE AND OXYTETRACYCLINE REVERSE THE POTENTIATION OF NEUROGENIC INFLAMMATION IN AIRWAYS OF BATS WITH MYCOPLASMA-PULMONIS INFECTION

Mycoplasma pulmonis infection in rats causes a chronic inflammatory ai rway disease. Along with extensive remodeling of the airway mucosa, ly mphocytic 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 releas ed from sensory nerves, produces an unusually large amount of plasma l eakage. These changes can be prevented or reduced by prophylactic trea tment with antibiotics, but it is unknown whether the extensive remode ling 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 week s later, the rats were treated daily with an antibiotic (oxytetracycli ne, 20 mg/kg intramuscularly), to reduce the number of infecting organ isms, or with an antiinflammatory steroid (dexamethasone, 0.5 mg/kg in traperitoneally), 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 anesthet ized and then challenged with substance P (5 mu g/kg intravenously). T he sham-treated rats had pathologic changes in their airways typical o f severe M. pulmonis infection, and had as much as a threefold increas e in substance P-induced plasma leakage. By comparison, after 4 wk of treatment with oxytetracycline or dexamethasone the chronic inflammati on was nearly resolved and the response to substance P was in the norm al range. Unexpectedly dexamethasone, like oxytetracycline, reduced th e 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 re versed by antibiotics or antiinflammatory steroids.