CHARACTERIZATION OF A LATE PHASE PULMONARY RESPONSE AFTER ANTIGEN CHALLENGE IN ALLERGIC SHEEP

Abstract

It was determined if allergic sheep undergo a dual bronchoconstriction in response to inhalation of antigen and whether these responses could be modified by cromolyn or glucocorticosteroids. In 8 conscious sheep with Ascaris suum hypersensitivity, mean pulmonary flow resistance (RL), dynamic lung compliance (Cdyn), thoracic gas volume (Vtg) and arterial O2 tension (PaO2) were determined prior to, immediately after, and from 2 to 8 h after and 24 h after inhalation challenge with A. suum antigen. Immediately after antigen challenge, mean specific lung resistance (SRL = RL .cntdot. Vtg) increased by 750% (P < 0.01) and mean Cdyn and PaO2 decreased by 55% (P < 0.01) and 37% (P < 0.01), respectively. By 5 h after challenge, mean SRL and PaO2 had returned to baseline values while mean Cdyn was still below baseline (-19%, P < 0.05). At 6.5 h, mean SRL increased again to 245% (P < 0.01) of baseline and remained significantly elevated through the 8th h. The average increase in mean SRL for the 6.5- to 8-h postchallenge period was 196%, with concomitant decreases in mean Cdyn and PaO2 of 29 and 10%, respectively. By 24 h, all values had returned to baseline. Control inhalation challenge with ragweed, an antigen to which sheep are not sensitive, did not significantly after SRL, Cdyn or PaO2 at any time during the 8-h observation period, indicating that the late response was antigen specific and not caused by circadian rhythm. Inhalation of cromolyn sodium (1 mg/kg) prior to antigen challenge blocked both the early and late responses. Methylprednisolone (15 mg/kg i.v.) 3 h after antigen challenge blocked the late response. In analogy to certain [human] subjects with allergic asthma, inhalation challenge with specific antigen produces early and late responses in allergic sheep both of which are linked to mast cell mediators.