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Infect. Immun. doi:10.1128/IAI.00878-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Intranasal IL-12 Therapy Inhibits Mycoplasma pneumoniae Clearance and Sustains Airway Obstruction in Murine Pneumonia

Departments of Pediatric Infectious Diseases, Internal Medicine, and Pathology, University of Texas Southwestern Medical Center, Dallas

^* To whom correspondence should be addressed. Email: robert.hardy{at}UTSouthwestern.edu.

	Abstract

Mycoplasma pneumoniae (Mp) is a leading cause of pneumonia and is associated with asthma. Evidence links Mp respiratory disease severity with IL-12 concentrations in respiratory secretions. We evaluated the effect of IL-12 therapy on microbiologic, inflammatory and pulmonary function indices of Mp pneumonia in mice. BALB/c mice were inoculated with Mp or SP4 broth. Mice were treated with intranasal IL-12 or placebo daily for 8 days starting on day 1 after inoculation. Mice were evaluated at baseline and at day 1, 3, 6 and 8 after therapy. Outcome variables included quantitative bronchoalveolar lavage (BAL) Mp culture, lung histopathologic score (HPS), BAL cytokine concentrations by ELISA (TNF-a, IFN-g, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, GM-CSF) and plethysmography, before and after methacholine. Mp-infected mice treated with IL-12 (MpIL12) were found to have significantly higher BAL Mp concentrations compared with Mp-infected mice treated with placebo (MpP) (p<0.001). MpIL12 had higher BAL concentrations of IL-12, IFN-g, TNF-a and IL-6, with IL-12 and IFN-g reaching statistical significance (p < 0.001). Airway obstruction was statistically elevated in MpIL12 mice compared to MpP mice (p = 0.048), while airway hyper-reactivity was also elevated in MpIL12 mice but did not reach statistical significance (p = 0.081). Lung parenchymal pneumonia subscore were significantly higher in MpIL12 (p<0.001), but no difference was found for overall HPS score even though a strong trend was noticed (p = 0.051). Treatment with intranasal IL-12 in experimental Mp pneumonia was associated with more severe pulmonary disease and less rapid microbiologic and histological resolution.

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