title: Lipoxins are potential endogenous antiinflammatory mediators in asthma.
abstract: 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.
authors.affiliation: Clinique des Maladies Respiratoires, INSERM U454-IFR 3, CHU, Montpellier, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonnans
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
authors.forename: Claude
authors.initials: C
authors.lastname: Chavis
authors.forename: Philippe
authors.initials: P
authors.lastname: Godard
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
mesh_terms: D001249:Asthma / Q000175:diagnosis* / Q000378:metabolism; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D001985:Bronchial Provocation Tests; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000378:metabolism*; D018836:Inflammation Mediators / Q000032:analysis*; D016209:Interleukin-8 / Q000032:analysis; D044045:Lipoxins; D008297:Male; D008969:Molecular Sequence Data; D011336:Probability; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry* / Q000166:cytology; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D006893:Hydroxyeicosatetraenoic Acids; D018836:Inflammation Mediators; D016209:Interleukin-8; D044045:Lipoxins; D012333:RNA, Messenger; C040527:lipoxin A4; C042651:lipoxin B4