Intranasal Interleukin-12 Therapy InhibitsMycoplasma pneumoniaeClearance and Sustains Airway Obstruction in Murine Pneumonia
- 1 February 2008
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 76 (2), 732-738
- https://doi.org/10.1128/iai.00878-07
Abstract
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.Keywords
This publication has 51 references indexed in Scilit:
- Respiratory Tract Infection with Mycoplasma pneumoniae in Interleukin-12 Knockout Mice Results in Improved Bacterial Clearance and Reduced Pulmonary InflammationInfection and Immunity, 2007
- Mycoplasma in severe asthmaJournal of Allergy and Clinical Immunology, 2006
- ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogensProceedings of the National Academy of Sciences, 2006
- NK Cells in Gamma-Interferon-Deficient Mice Suppress Lung Innate Immunity againstMycoplasmasppInfection and Immunity, 2005
- IL-4–independent pathways exacerbate methacholine-induced airway hyperreactivity during mycoplasma respiratory diseaseJournal of Allergy and Clinical Immunology, 2004
- Animal Model ofMycoplasma pneumoniaeInfection Using Germfree MiceClinical and Vaccine Immunology, 2002
- Impairment of Mycobacterial Immunity in Human Interleukin-12 Receptor DeficiencyScience, 1998
- Severe Mycobacterial and Salmonella Infections in Interleukin-12 Receptor-Deficient PatientsScience, 1998
- IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine ResponsesImmunity, 1996
- Mycoplasmas as Agents of Human DiseaseNew England Journal of Medicine, 1981