alcian-blue and Bronchiolitis--Viral

Respiratory syncytial virus-induced bronchiolitis has been linked to the development of allergy and atopic asthma. IL-12 and possibly IL-18 are central mediators orchestrating Th1 and/or Th2 immune responses to infection. To determine a possible role for IL-12 in regulating the immune response to acute respiratory syncytial virus infection, IL-12p40 gene-targeted (IL-12p40-/-) and wild-type mice were intratracheally infected with respiratory syncytial virus, and lung inflammatory and immune responses were assessed. Lung inflammation and mucus production were increased in the airways of IL-12p40-/- mice as compared with those of wild-type mice, concurrent with increased levels of the Th2 effector cytokines IL-5 and IL-13. Respiratory syncytial virus clearance and levels of Th1 effector cytokine IFN-gamma were not altered. Interestingly, IL-18, another mediator of IFN-gamma production, was significantly increased in the lungs of IL-12p40-/- mice early during the course of infection. Abrogation of IL-18-mediated signaling in IL-12p40-/- mice further enhanced Th2 immune response and mucus production in the airways during respiratory syncytial virus infection but failed to modulate IFN-gamma production or viral clearance. These findings implicate a role for IL-12 and IL-18 in modulating respiratory syncytial virus-induced airway inflammation distinct from that of viral clearance.

Topics: Adjuvants, Immunologic; Alcian Blue; Animals; Antibodies, Blocking; Bronchiolitis, Viral; Bronchoalveolar Lavage Fluid; CD3 Complex; Cytokines; Inflammation Mediators; Interferon-gamma; Interleukin-12; Interleukin-12 Subunit p40; Interleukin-18; Leukocyte Count; Lung; Lymphocyte Subsets; Mice; Mice, Inbred BALB C; Mice, Knockout; Mucus; Neutralization Tests; Periodic Acid-Schiff Reaction; Protein Subunits; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Th2 Cells; Up-Regulation; Viral Load