Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4)

Nat Med. 2002 Sep;8(9):1018-23. doi: 10.1038/nm748. Epub 2002 Aug 12.


The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A(4) (LXA(4)) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA(4) and increased expression of its receptor. Administration of a stable analog of LXA(4) blocked both airway hyper-responsiveness and pulmonary inflammation, as shown by decreased leukocytes and mediators, including interleukin-5, interleukin-13, eotaxin, prostanoids and cysteinyl leukotrienes. Moreover, transgenic expression of human LXA(4) receptors in murine leukocytes led to significant inhibition of pulmonary inflammation and eicosanoid-initiated eosinophil tissue infiltration. Inhibition of airway hyper-responsiveness and allergic airway inflammation with a stable LXA(4) analog highlights a unique counter-regulatory profile for the LXA(4) system and its leukocyte receptor in airway responses. Moreover, our findings suggest that lipoxin and related pathways offer novel multi-pronged therapeutic approaches for human asthma.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchitis / drug therapy*
  • Chemokine CCL11
  • Chemokines, CC / metabolism
  • Eosinophils / drug effects
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Interleukin-13 / metabolism
  • Interleukin-5 / metabolism
  • Leukotrienes / metabolism
  • Lipoxins*
  • Male
  • Methacholine Chloride
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Prostaglandins / metabolism
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Formyl Peptide*
  • Receptors, Lipoxin*


  • CCL11 protein, human
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Chemokines, CC
  • FPR2 protein, human
  • Hydroxyeicosatetraenoic Acids
  • Interleukin-13
  • Interleukin-5
  • Leukotrienes
  • Lipoxins
  • Prostaglandins
  • Receptors, Cell Surface
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • lipoxin A4
  • Methacholine Chloride