Viral exacerbations of allergen-induced pulmonary inflammation in pre-clinical models reportedly reduce the efficacy of glucocorticoids to limit pulmonary inflammation and airways hyper-responsiveness to inhaled spasmogens. However, exacerbations of airway obstruction induced by allergen challenge have not yet been studied. hPIV-3 (human parainfluenza type 3 virus) inoculation of guinea-pigs increased inflammatory cell counts in BAL (bronchoalveolar lavage) fluid and caused hyper-responsiveness to inhaled histamine. Both responses were abolished by treatment with either dexamethasone (20 mg/kg of body weight, subcutaneous, once a day) or fluticasone propionate (a 0.5 mg/ml solution aerosolized and inhaled over 15 min, twice a day). In ovalbumin-sensitized guinea-pigs, allergen (ovalbumin) challenge caused two phases of airway obstruction [measured as changes in sG aw (specific airways conductance) using whole body plethysmography]: an immediate phase lasting between 4 and 6 h and a late phase at about 7 h. The late phase, airway hyper-responsiveness to histamine and inflammatory cell counts in BAL were all significantly reduced by either glucocorticoid. Inoculation of guinea-pigs sensitized to ovalbumin with hPIV-3 transformed the allergen-induced airway obstruction from two transient phases into a single sustained response lasting up to 12 h. This exacerbated airway obstruction and airway hyper-responsiveness to histamine were unaffected by treatment with either glucocorticoid whereas inflammatory cell counts in BAL were only partially inhibited. Virus- or allergen-induced pulmonary inflammation, individually, are glucocorticoid-sensitive, but in combination generate a phenotype where glucocorticoid efficacy is impaired. This suggests that during respiratory virus infection, glucocorticoids might be less effective in limiting pulmonary inflammation associated with asthma.

1. In order to investigate the cellular mechanism of glucocorticoid resistance in chronic asthma, peripheral blood mononuclear cells (MNC) from asthmatic patients were cultured in soft agar. 2. Cells from patients known to be clinically sensitive to glucocorticoid therapy did not differ significantly from those of clinically resistant patients in terms of their immunophenotype or the number of colonies generated by culture in the presence of phytohaemagglutinin. 3. The glucocorticoid methylprednisolone (MP) at low concentration (10 nmol/l) inhibited colony growth from cells of glucocorticoid-sensitive patients, whereas there was much less inhibition of colony growth from resistant patients' cells. 4. In a small prospective study inhibition of colony growth by methylprednisolone in vitro correlated with the subsequently determined sensitivity of the patients' asthma to glucocorticoid therapy. 5. Assessment in vitro of glucocorticoid sensitivity may help to predict which patients may be spared ineffectual glucocorticoid medication. The results raise the possibility that peripheral blood mononuclear cells may respond to glucocorticoid in a similar manner to cells involved in the pathogenesis of asthma.