Lipoxin A₄ reduces house dust mite and TNFα-induced hyperreactivity in the mouse trachea

Lipoxin A₄ (LXA₄) is considered a specialised pro-resolving mediator that decreases inflammation: however, pro-inflammatory effects have been described in the airways. Here, we investigated whether LXA₄ could influence airway hyperreactivity induced in mouse trachea by house dust mite extract (HDM) or TNFα. Intranasal instillation of HDM caused a serotonin (5-HT) mediated airway hyperreactivity ex vivo (E_max: 78.1 ± 16.2 % versus control 12.8 ± 1.0 %) that was reduced by LXA₄ installation one hour prior to HDM (E_max: 49.9 ± 11.4 %). Also, in isolated tracheal segments cultured for four days, HDM induced a hyperreactivity (E_max: 33.2 ± 3.1 % versus control 9.0 ± 0.7 %) that was decreased by LXA₄ (E_max: 18.7 ± 1.5 %). One part of the HDM-induced hyperreactivity could be inhibited by the TNFα-inhibitor etanercept. TNFα-induced upregulation of 5-HT responses (E_max: 51.3 ± 1.2 % versus control 13.9 ± 0.5 %) was decreased by 10-1000 nM LXA₄. In precontracted tracheal segments, LXA₄ had no relaxing effect. Overall, LXA₄ was able to decrease airway hyperreactivity induced by both HDM and TNFα, thus having a sub-acute anti-inflammatory effect in airway inflammation.