Journal of Applied Physiology, Vol 64, Issue 5 1773-1778, Copyright © 1988 by American Physiological Society
Toluene diisocyanate-induced airway hyperreactivity in guinea pigs depleted of granulocytes
W. Cibulas Jr, S. M. Brooks, C. G. Murlas, M. L. Miller and R. T. McKay
Department of Medicine, University of Cincinnati School of Medicine, Ohio 45267.
The influence of cyclophosphamide-induced granulocyte depletion on toluene
diisocyanate (TDI)-related changes in airway reactivity and pathology was
assessed in guinea pigs. Twelve cyclophosphamide-treated and 12 control
animals comprising each group were studied physiologically before and 2 h
after a single 10-min exposure to 3 ppm of TDI. Reactivity was determined
in intact unanesthetized animals by measuring specific airway conductance
before and during intravenous acetylcholine infusion. After testing,
tracheal tissue for light microscopic examination was obtained from three
hyperreactive guinea pigs in each exposed group and compared with tissue
from treated and control animals (n = 3 each) that had not been TDI
exposed. Cyclophosphamide treatment caused substantial decreases in both
circulating and airway granulocyte counts. However, the incidence and
degree of bronchial hyperreactivity that occurred 2 h post-TDI was similar
in the untreated and treated groups. Our results indicate that TDI-induced
bronchial hyperreactivity 1) occurs shortly after a brief high
concentration exposure and 2) appears independent of circulating or airway
granulocyte counts.
