Intranasal interleukin-12 therapy inhibits Mycoplasma pneumoniae clearance and sustains airway obstruction in murine pneumonia.
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.
Department of Internal Medicine and Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA.
C M
CM
Salvatore
M
M
Fonseca-Aten
K
K
Katz-Gaynor
A M
AM
Gomez
R D
RD
Hardy
D000281:Administration, Intranasal; D000402:Airway Obstruction / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis; D005260:Female; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000276:immunology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009177:Mycoplasma pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D010919:Placebos / Q000008:administration & dosage; D010991:Plethysmography; D011019:Pneumonia, Mycoplasma / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D010919:Placebos; D018664:Interleukin-12