Pentoxifylline does not alter the response to inhaled grain dust.
Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin appears to be the principal agent in grain dust causing airway inflammation and airflow obstruction following grain dust inhalation. 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 placebo (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/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 FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines 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 interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.
Jagielo
P J
PJ
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242-1081, USA.
Watt
J L
JL
Quinn
T J
TJ
Knapp
H R
HR
Schwartz
D A
DA
D000280:Administration, Inhalation; D000328:Adult; D000402:Airway Obstruction / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D018592:Cross-Over Studies; D004391:Dust / Q000009:adverse effects*; D002523:Edible Grain; D004731:Endotoxins / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D011014:Pneumonia / Q000503:physiopathology / Q000517:prevention & control*; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors; D014797:Vital Capacity; D003313:Zea mays
D004391:Dust; D004731:Endotoxins; D016209:Interleukin-8; D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline