TRFK-5 reverses established airway eosinophilia but not established hyperresponsiveness in a murine model of chronic asthma

We studied the effects of an anti-interleukin (IL)-5 monoclonal antibody (T RFK-5) or dexamethasone (DEX) to reverse already established airway hyperre sponsiveness (AHR) and tissue eosinophilia in a Schistosoma mansoni antigen -sensitized and airway-challenged mouse model of chronic asthma. In this mo del at 4 d after antigen challenge there is dramatic bronchoalveolar lavage fluid (BAL) eosinophilia, AHR to intravenous methacholine (MCh), and histo logic evidence of peribronchial eosinophilic infiltration and mucoid cell h yperplasia. These changes persist for up to 2 wk after antigen challenge. T reatment with DEX from Days 4 through 10 significantly reduced established airway eosinophilia compared with animals sham-treated with saline from Day s 4-10 (120 +/- 29 eosinophils/mu l BAL for DM-treated mice versus 382 +/-: 60 eosinophils/mu l BAL for sham-treated animals, p < 0.01). DEX-treated m ice also had dramatically reduced mucoid cell hyperplasia, and airway respo nsiveness returned to normal, in contrast, TRFK-5 given during the same tim e period reduced airway eosinophilia (86 +/- 32 eosinophils/mu l BAL versus 382 +/- 60 eosinophils/mu l BAL, p < 0.01) but did not reduce goblet cell hyperplasia or reverse already established AHR. Treatment with DEX but not TRFK-5 also inhibited interferon gamma (IFN-gamma) content of BAL fluid (0. 49 +/- 0.09 ng/ml BAL fluid for DEX versus 1.50 +/- 0.24 ng/ml BAL fluid an d 1.36 +/- 0.13 ng/ml BAL fluid for TRFK-5 and sham-treated mice, respectiv ely, both p < 0.001 versus DEX). Thus, treatment with DEX reduces establish ed eosinophilic airway inflammation and AHR in S. mansoni-sensitized and ai rway-challenged mice but treatment with TRFK-5 reversed established eosinop hilia without ameliorating established AHR. Together, these data suggest th at once airway inflammation develops, neutralizing the effects of IL-5 or r educing eosinophilia alone may not result in inhibiting established AHR in atopic asthma.