PENTOXIFYLLINE DOES NOT ALTER THE RESPONSE TO INHALED GRAIN DUST

Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophi l sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown tha t endotoxin appears to be the principal agent in grain dust causing ai rway inflammation and airflow obstruction following grain dust inhalat ion. To determine whether PTX affects the physiologic and inflammatory events following acute grain dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placeb o (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), us ing a single-blinded, crossover design, Subjects received PTX (1,200 m g/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and F VC occurred following CDE exposure in both groups, but there were no s ignificant differences in the frequency of symptoms or percent decline s from baseline in the FEV1 and FVC at any of the time points measured in the study, Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-alpha, and interle ukin-8 concentrations were measured 4 h following exposure to CDE in b oth the PTX- and PL-treated subjects, but no significant differences w ere found between treatment groups, These results suggest that pretrea tment with PTX prior to inhalation of CDE, in the doses used in this s tudy, does not alter the acute physiologic or inflammatory events foll owing exposure to inhaled CDE.