BACKGROUND: There is evidence that the cytokine IL-5 is a prominent feature of airway inflammation in asthma. OBJECTIVE: The aim of this study was to determine whether exogenous IL-5 could cause changes in lung physiology, the early and late airway response after antigen challenge, and airway inflammation in rats that do not have a propensity to develop these changes after sensitization and challenge. METHOD AND RESULTS: Intratracheal administration of IL-5 to ovalbumin sensitized Brown Norway SSN rats increased the airway responsiveness to methacholine (AHR) 20 hours after administration of IL-5 at the same time as an increase in neutrophils occurred in the lung lavage. This effect was dose dependent and was not caused by endotoxin. Concurrent intratracheal administration of 50 ng of anti-IL-5 monoclonal antibody with 10 microg of recombinant human IL-5 decreased the AHR and neutrophil influx. Pretreatment with 3 microg of IL-5 had no effect on the early and late airway response or on AHR after ovalbumin challenge. However, IL-5 increased lung re-sistance 20 hours after antigen challenge. Although total lung cells and differential counts did not differ significantly 8 hours after antigen challenge, the blood lymphocyte CD4/CD8 ratio decreased in IL-5 pretreated rats (P
Inhibition of antigen-induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL-3, IL-5, GM-CSF receptors in a rat model of allergic asthma.
Airway obstruction, hyperresponsiveness, and the accumulation and persistence within the airways of inflammatory cells characterize asthma. Interleukin (IL)-3, granulocyte macrophage colony- stimulating factor (GM-CSF), and IL-5 are among several cytokines that have been shown to be increased in asthma and to contribute to atopic inflammation. They mediate their effect via receptors that have a common beta subunit (beta(c)). We hypothesized that blocking of this common beta(c) would impair the airway response to antigen. We report that an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) found to specifically inhibit transcription of the beta(c) in rat bone marrow cells also caused inhibition of beta(c) mRNA expression and of immunoreactive cells within the lungs of Brown Norway (BN) rats when injected intratracheally (p