Temporal association between airway hyperresponsiveness and airway eosinophilia in ovalbumin-sensitized mice

The temporal association between airway inflammation and airway hyperrespon siveness (AHR) has been analyzed in BALB/c mice sensitized to, and subseque ntly exposed to, a single intranasal challenge of ovalbumin (OVA). In OVA-s ensitized/challenged animals only a small increase in responsiveness to met hacholine (MCh) was seen at 8 h, peaked at 24 to 48 h, and resolved by 96 h . An early bronchoalveolar lavage fluid (BALF) neutrophil infiltrate (peaki ng at 8 h postchallenge; similar to 72% total cells was observed) that retu rned to baseline by 48 h. BALF eosinophil numbers did not increase until 48 h (similar to 32% of total cells), peaked at 96 h (similar to 38% total ce lls), and remained elevated at 8 d (similar to 27% total cells). Airway tis sue eosinophilia preceded changes in BALF. Eosinophil peroxidase (EPO) leve ls in BALF were elevated in OVA-sensitized/challenged mice at 48 h only. BA LF TNF-alpha levels peaked at 8 h, whereas IL-5 and IL-4 levels peaked at 2 4 h. IL-13 levels were increased at both 24 and 48 h. Mucus-positive cells were not observed in the airway epithelium until 48 h. Administration of IL -5 or VLA-4 antibody prior to OVA challenge prevented the development of AH R in sensitized mice as well as BALF and tissue eosinophilia. These data id entify a temporal association between Th2 cytokine production, tissue eosin ophil infiltration and activation, and, importantly, both the development a nd resolution kinetics of AHR. Moreover, the antibody studies further suppo rt the association of eosinophilia with the pathogenesis of AHR.