IL-12 reduces the severity of Sendai virus-induced bronchiolar inflammation and remodeling

The goal of this research was to determine whether differential pulmonary IL-12 gene expression controls susceptibility to Sendai virus-induced chronic airway inflammation and fibrosis in inbred rat strains. Sendai virus-resistant F344 rats and susceptible BN rats were studied from 1 to 14 days following virus inoculation. F344 rats had 3.4-fold higher IL-12 mRNA levels detected by real-time PCR in lung than BN rats as early as two days following inoculation. This increase in mRNA was associated at two days with increased total IL-12 protein and with a 2-fold increase in numbers of bronchiolar, OX-6-positive dendritic cells and an increased number of IL-12 p40-positive, bronchiolar macrophages and dendritic cells (p<0.05). Virus-susceptible BN rats treated with 3 mug of recombinant, mouse IL-12 intraperitoneally at the time of virus inoculation had a 22.1% decrease in severity of chronic bronchiolar inflammation and a 23.8% decrease in fibrosis compared to virus-inoculated BN rats treated with saline. IL-12 treatment induced increased IFN-gamma mRNA and protein expression after virus inoculation (p<0.05). The results demonstrate that there is differential pulmonary IL-12 gene expression between virus-susceptible and resistant rat strains and that IL-12 treatment can provide significant protection from virus-induced chronic airway inflammation and remodeling during early life.