The effect of parasite antigen on experimentally induced ‘asthma’ in lambs

Abstract

There is a worldwide consensus that the incidence of asthma and allergy is exhibiting a rising trend in western societies. There is also epidemiological evidence that New Zealand children raised on farms are less likely to experience asthma than those in urban environments. The aims of this study were to firstly set up a sheep model for the study of asthma and secondly, examine the effect of intrauterine and neonatal inoculation of an asthma-causing allergen [house dust mite (HDM) - Dermatophagoides pteronyssinus] or helminth antigen [Trichostrongylus colubriformis L₃ (TCL₃)] on the development of experimentally induced ‘asthma’ in sheep. Feti or neonates of twin-bearing ewes (n=22) were treated with TCL₃, HDM or PBS (control) given by lavage following hysterectomy (prenatal). At ten months of age, these lambs with additional control lambs (n=6) were sensitized by the subcutaneous inoculation of HDM and later challenged intra-bronchially with HDM, using a fibre-optic bronchoscope. At birth, lambs treated in utero with HDM antigen had the highest levels of HDM-specific IgE compared with lambs treated prenatally with TCL₃ or PBS. HDM-specific IgE levels for the different treatment groups decreased significantly over the 4 week postnatal period but not their HDM-specific IgG₁.Twin lambs (control and treated) showed similar levels of specific–HDM antibody after suckling from the same ewe. At 10 months of age following sensitization and challenge, there were no significant differences among white blood cells of the peripheral blood but cytology of bronchoaveolar lavage fluid following challenge showed that treatment with HDM antigen had a significant (P=0.003) effect on increasing lymphocyte percentage in the left lung of the experimental sheep but not in the right (PBS treated) lung. The atopic TCL₃ and PNTCL₃ sheep had significantly less eosinophils (P=0.05) in the left (treated) lung compared with the right (control) lung BAL, 24 h and 48 h after challenge. The atopic sheep from the other groups did not show any significant differences between their left and right lungs. Gross pathology of the sheep lung showed hepatisation of both treated and control lungs of the sheep with a trend for the animals treated prenatally (with either TCL₃ or HDM, or their controls) to have less extensive lung changes. Histological examination indicated that prenatal (TCL₃) or neonatal (PNTCL₃) exposure to helminth antigen compared with HDM and control resulted in less inflammation of the lung tissue after sensitization and challenge with HDM antigen. This study showed that research sheep can be used as a model for asthma studies and that exposure of lambs to a helminth antigen in utero or as neonates suppress inflammatory responses to asthma-causing allergen in the lungs, later in life.