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Infection and Immunity, February 2008, p. 732-738, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.00878-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Intranasal Interleukin-12 Therapy Inhibits Mycoplasma pneumoniae Clearance and Sustains Airway Obstruction in Murine Pneumonia{triangledown}

C. M. Salvatore,1 M. Fonseca-Aten,1 K. Katz-Gaynor,1 A. M. Gomez,2 and R. D. Hardy1,3*

Departments of Pediatric Infectious Diseases,1 Internal Medicine,3 Pathology, University of Texas Southwestern Medical Center, Dallas, Texas2

Received 28 June 2007/ Returned for modification 6 August 2007/ Accepted 8 November 2007

Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentrations in respiratory secretions. We evaluated the effects of IL-12 therapy on microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in mice. BALB/c mice were inoculated with M. pneumoniae 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 on days 1, 3, 6, and 8 after therapy. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-{alpha}], gamma interferon [IFN-{gamma}], IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and granulocyte-macrophage colony-stimulating factor), and plethysmography, both before and after methacholine treatment. M. pneumoniae-infected mice treated with IL-12 (MpIL12 mice) were found to have significantly higher BAL M. pneumoniae concentrations than those of M. pneumoniae-infected mice treated with placebo (MpP mice) (P < 0.001). MpIL12 mice had higher BAL concentrations of IL-12, IFN-{gamma}, TNF-{alpha}, and IL-6, with differences in IL-12 and IFN-{gamma} concentrations reaching statistical significance (P < 0.001). Airway obstruction was statistically elevated in MpIL12 mice compared to that in MpP mice (P = 0.048), while airway hyperreactivity was also elevated in MpIL12 mice but did not reach statistical significance (P = 0.081). Lung parenchymal pneumonia subscores were significantly higher in MpIL12 mice (P < 0.001), but no difference was found for overall HPS, even though a strong trend was noticed (P = 0.051). Treatment of experimental M. pneumoniae pneumonia with intranasal IL-12 was associated with more severe pulmonary disease and less rapid microbiologic and histological resolution.

* Corresponding author. Mailing address: Department of Internal Medicine and Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063. Phone: (214) 648-3720. Fax: (214) 648-2961. E-mail: robert.hardy{at}UTSouthwestern.edu

{triangledown} Published ahead of print on 26 November 2007.

Editor: R. P. Morrison

Infection and Immunity, February 2008, p. 732-738, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.00878-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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