The Effects of Lipoxin A₄on Airway Responses in Asthmatic Subjects

Abstract

This study was performed to determine whether lipoxin A4 (LXA4) inhalation in asthmatic subjects has an effect on airways response. Eight subjects (six asthmatic, two normal) attended for bronchial inhalation challenge with LXA4. In three of these subjects (two asthmatics, one normal) blood pressure, pulse, and symptoms before and after challenge were recorded. Subsequently five male patients with mild asthma (22 to 34 yr of age) reattended for bronchial inhalation challenge with either leukotriene C4 (LTC4) or the combination of LTC4 and 1 x 10(-4) M LXA4. After inhalation of each dose of agonist SGaw and V25 were measured. Airway responsiveness was determined by the concentration of agonist in the nebulizer required to induce a 35% fall in SGaw (PC35). There was no effect of LXA4 inhalation on SGaw, V25, blood pressure, pulse, or symptoms. There was a significant shift of the SGaw and V25 dose-response curve to the right after inhalation challenge with LTC4 combined with 1 x 10(-4) M LXA4 as compared with that after inhalation challenge with LTC4 alone (p less than 0.01 and p less than 0.025, respectively). Thus, LXA4 may modulate LTC4-induced airway obstruction and may act as an endogenous sulfidopeptide leukotriene receptor antagonist.

Mechanisms in anti-inflammation and resolution: the role of lipoxins and aspirin-triggered lipoxins

“…Currently, only limited data on the effects of lipoxins in clinical investigation are available. Nevertheless, in asthmatic patients, inhalation of LXA 4 inhibits LTC 4 -induced airway obstruction (32). Lipoxins are generated from endogenous sources during provocative challenge in asthma (6), suggesting that they may play roles in modulating airway hyperresponsiveness.…”

Interactions Between Lipoxin A4, the Stable Analogue 16‐phenoxy‐lipoxin A4 and Leukotriene B4 in Cytokine Generation by Human Monocytes

“…In vivo, LXA 4 is a modest vasodilator at relatively high micromolar levels [16][17][18] and at nanomolar levels is a potent inhibitor of PMN infiltration in inflamed renal tissue in a glomerulonephritis animal model [19]. A potentially important clinical role for LXA 4 in humans is the observation that, when administrated via inhalation, LXA 4 blocks airway obstruction in asthmatic subjects [20]. The mechanisms for the ability of LXA 4 to specifically antagonize LTB 4 -induced responses, both in vivo and in vitro, are still unfolding.…”

Selectivity of Recombinant Human Leukotriene D4, Leukotriene B4, and Lipoxin A4 Receptors with Aspirin-Triggered 15-epi-LXA4 and Regulation of Vascular and Inflammatory Responses

“…13,15 It is of interest then that both LX and ATL functionally antagonize LTD 4 /LTC 4 -induced up-regulation of P-selectin in endothelial cells 16 and inhalation of LXA 4 antagonizes LTC 4 -induced airway obstruction in asthmatics. 17 Thus, both LX and ATL are of interest as mediators because they might act as local endogenous regulators of LTD 4 /LTC 4 within the vasculature of lung and kidney 2,8,10,16 as well as control leukocyte trafficking. 2,11 Recently the first human CysLT receptor and human LTB 4 receptors (BLT) were cloned and identified 14,18,19 using rank order potencies of agonists and antagonists, and a human BLT was overexpressed in transgenic mice.…”