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.
Department of Pathobiology, College of Veterinary Medicine, University of Florida, USA. astone@dental.ufl.edu
Amy E S
AE
Stone
Steeve
S
Giguere
William L
WL
Castleman
D000818:Animals; D001988:Bronchiolitis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D005355:Fibrosis; D007371:Interferon-gamma / Q000187:drug effects / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism / Q000821:virology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D010253:Respirovirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D029082:Sendai virus / Q000472:pathogenicity*
D018664:Interleukin-12; D007371:Interferon-gamma