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

Abstract

Background and objective: While 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. Methods: We used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1β for 2 days. 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. Results: Culture with tumour necrosis factor and interleukin-1β increased airway narrowing to acetylcholine but did not affect the bronchodilatory response to DI. Conclusion: The 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.

Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats

“…Despite the presence of alveolar edema and bronchoconstriction, these alterations were not sufficient to impair blood gases and lung mechanics. Bronchoconstriction might be explained by increased airway narrowing due to circulating proinflammatory cytokines [ 45 ]. In patients with brain injury, bronchoconstriction with increased airway resistance is common [ 46 ].…”

High fat diet induces airway hyperresponsiveness in mice

“…Previous data showed that IL-1β knockout or receptor blockade abolished an increase of AHR in mice with severe diet-induced obesity 6 . Furthermore, IL-1β may directly potentiate cholinergic bronchoconstriction 12 . There was no signs of eosinophilic or neutrophilic inflammation in BAL associated with obese asthma 13 , 14 and there was no increase in TH2 cytokines like IL-4.…”

Special Issue: Under the Hood—A Look at the Mechanisms Regulating Lung Function

“…According to results from isolated airway smooth muscle measurements [3], when a critical threshold of strain (3.3%) was exceeded, contractile force in an activated muscle could be significantly reduced for a prolonged period of time. The results from activated airway segments subject to pressure oscillation also indicated the existence of such a threshold, which, when exceeded, abrupt bronchodilation occurred [4]. The strain in airway smooth muscle when lung volume increases from FRC to TLC estimated from the studies reviewed by Boss e on average is much greater than the critical threshold of 3.3%, suggesting that the bronchodilatory effect of deep inspiration observed in healthy human subjects [5,6] may be related to the loss of contractility in airway smooth muscle.…”