Pentoxifylline attenuates LPS-induced bronchial hyperresponsiveness but not the increase in exhaled nitric oxide

Inhaled endotoxin (LPS) may cause a transient increase in airway responsiveness, possibly through a cytokine-mediated airway inflammation, which is associated with an increase in nitric oxide synthesis and release.

We wondered whether pentoxifylline (PTX), which may attenuate cytokine release induced by LPS, could inhibit LPS-induced increase in airway responsiveness.

Methacholine (Mch) bronchial responsiveness was assessed 2 and 24 h after saline or LPS inhalation in eight subjects with bronchial hyperresponsiveness (PD20FEV1 610 +/- 53 micrograms), treated with iv saline or PTX, in a double-blind crossover design. Nitric oxide (NO) in the exhaled air, which was expected to increase after LPS inhalation, and PEFR values were also measured at baseline, hourly for 6 h and 24 h later.

After LPS inhalation PEFR decreased significantly compared with placebo inhalation, reaching a maximum decrease of 11.25 +/- 1.05 and 4.5 +/- 0.84% of baseline, at 2 h, respectively during saline and PTX infusion, P < 0.001. Exhaled NO were elevated after LPS compared with placebo inhalation at 1 h (35.6 +/- 4.8 vs 18 +/- 2.8 ppb, P < 0.001), with no difference during saline or PTX infusion. Exhaled NO remained elevated until the 6th hour. PD20FEV1 2h after LPS inhalation was significantly lower than after placebo inhalation both during saline infusion (234 +/- 29 vs 625 +/- 62 micrograms, P < 0.001) and during PTX infusion (441 +/- 47 vs 616 +/- 48 micrograms, P < 0.001), the difference between saline and PTX being significant (P < 0.01). At 24 h no difference in PEFR, PD20FEV1 and exhaled NO was observed in comparison with pre-study values.

PTX attenuates both the decrease in airway patency and the increase in bronchial responsiveness induced by LPS inhalation, without any significant change in exhaled NO, which is increased by LPS inhalation.