Lipoxins are potential endogenous antiinflammatory mediators in asthma

Am J Respir Crit Care Med. 2002 Jun 1;165(11):1531-5. doi: 10.1164/rccm.200201-053OC.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / diagnosis*
  • Asthma / metabolism
  • Base Sequence
  • Biomarkers / analysis
  • Bronchial Provocation Tests
  • Female
  • Humans
  • Hydroxyeicosatetraenoic Acids / analysis
  • Hydroxyeicosatetraenoic Acids / metabolism*
  • Inflammation Mediators / analysis*
  • Interleukin-8 / analysis
  • Lipoxins*
  • Male
  • Molecular Sequence Data
  • Probability
  • Prospective Studies
  • RNA, Messenger / analysis*
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sampling Studies
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Sputum / chemistry*
  • Sputum / cytology
  • Statistics, Nonparametric

Substances

  • Biomarkers
  • Hydroxyeicosatetraenoic Acids
  • Inflammation Mediators
  • Interleukin-8
  • Lipoxins
  • RNA, Messenger
  • lipoxin A4
  • lipoxin B4