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.