Local cytokine messenger ribonucleic acid expression and in vitro allergic late phase responses in Brown-Norway rats.
The events subsequent to antigen challenge in allergic asthmatics involve the synthesis of pro-inflammatory cytokines. However, little is known how cytokine gene activation prior to allergen challenge may influence this series of events, nor how cytokine gene expression is related to antigen-induced alterations in lung function. Using a novel in vitro explant technique, we hypothesized that the local expression of cytokines influenced the development of antigen-induced late-onset airway responses, and that alterations in cytokine messenger ribonucleic acid (mRNA) expression were associated with antigen-induced changes in airway luminal area. Explants were prepared from excised lungs of ovalbumin-sensitized Brown-Norway rats. Airways were challenged by direct application of ovalbumin or an irrelevant control antigen. Cryostat sections of explants were used for in situ hybridization and mRNA for interleukin (IL)-2, IL-4 and interferon (IFN)-gamma were detected using radiolabelled probes. We found that the presence of high numbers of cells expressing IFN-gamma and IL-2 mRNA within the airways attenuated the development of antigen-induced late airway responses in sensitized rat lung explants. Furthermore, we observed that cytokine mRNA for IL-4 was significantly increased following allergen exposure in sensitized lung explants exhibiting late airway responses. This study implicates the local expression of interferon-gamma and interleukin-2 messenger ribonucleic acid in the failure of sensitized rat lung explants to exhibit late airway responses, and provides evidence linking local interleukin-4 messenger ribonucleic acid expression to the sequelae of events occurring as a result of antigen exposure within the airways.
Minshall
E M
EM
Meakins-Christie Laboratories, Montreal Chest Institute Research Center, Royal Victoria and Montreal General Hospitals, McGill University, Quebec, Canada.
Dandurand
R J
RJ
Hamid
Q
Q
Eidelman
D H
DH
D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D000941:Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin