Study objectives: To study the effects of extracts of
brewery dust on isolated guinea pig tracheal smooth muscle in
vitro. Design: Parallel pharmacologic
intervention on guinea pig tracheal rings that were obtained from the
same animal. Setting: Mount Sinai School of Medicine,
Department of Pulmonary Medicine. Material: The
isolated guinea pig tracheal tissue of 18 guinea pigs.
Interventions: Pretreatment of guinea pig rings by
mediator-modifying agents before challenge with the brewery dust
extracts. Measurements and results: The effect of
brewery dust extracts on isolated guinea pig tracheal smooth muscle was
studied using water-soluble extracts of dust obtained from brewery
materials, including hops, barley, and brewery yeast. Dust extracts
were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related
contractions of nonsensitized guinea pig tracheas were demonstrated
using these extracts. The dust extracts contained significant
quantities of bacterial components (eg, endotoxin and
n-formyl-methionyl-leucyl-phenylalanine), but these agents were not
thought to contribute directly to the constrictor effect of the dusts.
Pharmacologic studies were performed by pretreating guinea pig tracheal
tissue with the following drugs known to modulate smooth muscle
contraction: atropine; indomethacin; pyrilamine; LY171883;
nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8.
The constrictor effects of the dust extracts were inhibited by a wide
variety of agents, the patterns of which depended on the dust extract.
Atropine consistently and strikingly reduced the contractile effects of
these extracts. These observations may suggest an interaction of the
extracts with parasympathetic nerves or, more directly, with muscarinic
receptors. The inhibition of contraction by the blocking of other
mediators was less effective and varied with the dust extract.
Conclusions: We suggest that brewery dust extracts
cause a dose-related airway smooth muscle constriction by
nonimmunologic mechanisms involving a variety of airway mediators and,
possibly, cholinergic receptors. This effect is not dependent on
presensitization of the guinea pigs.