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.
Salvatore
C M
CM
Department of Internal Medicine and Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA.
Fonseca-Aten
M
M
Katz-Gaynor
K
K
Gomez
A M
AM
Hardy
R D
RD
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