TNF and IL-1β exposure increases airway narrowing but does not alter the bronchodilatory response to deep inspiration in airway segments

Background and objectiveWhile chronic inflammation of the airway wall and the failure of deep inspiration (DI) to produce bronchodilation are both common to asthma, whether pro-inflammatory cytokines modulate the airway smooth muscle response to strain during DI is unknown. The primary aim of the study was to determine how an inflammatory environment (simulated by the use of pro-inflammatory cytokines) alters the bronchodilatory response to DI. MethodsWe used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1 for 2days. A custom-built servo-controlled syringe pump and pressure transducer was used to measure airway narrowing and to simulate tidal breathing with intermittent DI manoeuvres. ResultsCulture with tumour necrosis factor and interleukin-1 increased airway narrowing to acetylcholine but did not affect the bronchodilatory response to DI. ConclusionThe failure of DI to produce bronchodilation in patients with asthma may not necessarily involve a direct effect of pro-inflammatory cytokines on airway tissue. A relationship between inflammation and airway hyper-responsiveness is supported, however, regulated by separate disease processes than those which attenuate or abolish the bronchodilatory response to DI in patients with asthma. It is unclear whether the attenuated bronchodilatory response to deep inspiration in asthma is related to an inflammatory environment. Using whole bronchial segments in vitro, we show that culture with pro-inflammatory cytokines, tumour necrosis factor and interleukin-1, increases airway narrowing but does not affect the bronchodilatory response to deep inspiration.