Lipoxins are potential endogenous antiinflammatory mediators in asthma.
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.
Bonnans
Caroline
C
Clinique des Maladies Respiratoires, INSERM U454-IFR 3, CHU, Montpellier, France.
Vachier
Isabelle
I
Chavis
Claude
C
Godard
Philippe
P
Bousquet
Jean
J
Chanez
Pascal
P
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
D015415:Biomarkers; D006893:Hydroxyeicosatetraenoic Acids; D018836:Inflammation Mediators; D016209:Interleukin-8; D044045:Lipoxins; D012333:RNA, Messenger; C040527:lipoxin A4; C042651:lipoxin B4