Production of early and late pulmonary responses with inhaled leukotriene D 4 in allergic sheep

Abstract

Some allergic sheep respond to inhalation of Ascaris suum antigen with both immediate and late increases in airflow resistance (late response). The mechanism of the late response is unknown but recent evidence suggests that the initial generation of slow-reacting substance of anaphylaxis (SRS-A) immediately after antigen challenge is a necessary pre-requisite for the physiologic expression of this late response. Based on this evidence we hypothesized that airway challenge with leukotriene D 4 (LTD 4), an active component of SRS-A would produce acute and late airway responses in allergenic sheep similar to those observed with antigen. In five allergic sheep with documented early and late pulmonary responses to Ascaris suum antigen, inhalation of leukotriene D 4 aerosol (delivered dose {mean ±SE} 0.55±0.08 ug) resulted in significant early and late increases in specific lung resistance (SR L). In three allergic sheep which only demonstrated acute responses to antigen, LTD 4 aerosol (delivered dose 0.59±0.09ug) only produced an acute increase in SR L. In the late responders pretreatment with aerosol cromolyn sodium (1 mg/kg) did not affect the acute response but blunted the late increase in SR L. Pretreatment with aerosol FPL-57231 (1% w/v solution) completely blocked both the acute and late responses. These data support the hypothesis that initial release of LTD 4 in the airways of sensitive animals is important for the physiologic expression of the late response.