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Lipoxins Are Potential Endogenous Antiinflammatory Mediators in Asthma

Clinique des Maladies Respiratoires, INSERM U454-IFR 3, CHU, Montpellier, France

Correspondence and requests for reprints should be addressed to Dr. Pascal Chanez, Hôpital Arnaud de Villeneuve, 371 Av du Doyen Gaston Giraud, 34295 Montpellier, Cedex 5, France. E-mail: chanez{at}montp.inserm.fr

Lipoxins, endogenous eicosanoids biosynthetized in vivo at inflammation sites, are potential antiinflammatory mediators. Subjects with severe asthma present chronic inflammation of the airways despite long-term treatment with oral glucocorticoids. Therefore it is of interest to investigate the potential antiinflammatory effects of lipoxin A₄ (LXA₄) and lipoxin B₄ (LXB₄) that could attenuate chronic inflammation. In a first time, we detected interleukin (IL)-8 and LXA₄ in supernatants of induced sputum. IL-8 was heightened in severe asthma (p = 0.001), whereas high concentrations of lipoxin A₄ were present in mild asthma (p = 0.001). We then studied the effects of LXA₄ on IL-8 released in vitro. Nanomolar concentrations of LXA₄ and LXB₄ inhibited the IL-8 released by peripheral blood mononuclear cells from the two groups of patients with asthma: a maximal inhibition of 29.4% (p < 0.01) was observed for patients with mild asthma, and 41.5% inhibition (p < 0.001) for patients with severe asthma at 1 nM and 100 nM LXA₄ concentrations, respectively. Polymerase chain reaction analysis indicated that peripheral blood mononuclear cells from patients with asthma expressed the LXA₄ receptor mRNA. Moreover, pertussis toxin reversed LXA₄- and LXB₄-inhibited IL-8 release. These findings suggest that lipoxins have potential antiinflammatory action in asthma.

Key Words: lipoxins • asthma • inflammation • peripheral blood mononuclear cells • interleukin-8

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