Tags

Type your tag names separated by a space and hit enter

Leukotrienes in respiratory disease.
Paediatr Respir Rev. 2001 Sep; 2(3):238-44.PR

Abstract

Arachidonic acid metabolism via 5-lipoxygenase gives rise to a group of biologically active lipids known as leukotrienes: leukotriene B(4), which is a potent activator of leukocyte chemotaxis, and cysteinyl leukotrienes (leukotriene C(4), D(4)and E(4)) which account for the spasmogenic activity previously described as slow-reacting substance of anaphylaxis. The biological actions of leukotrienes and the observations that leukotrienes are synthesised in the lung following antigen provocation and are elevated in asthma, stimulated considerable activity in the pharmaceutical industry to find drugs that modulate the synthesis or actions of leukotrienes. Three cysteinyl leukotriene antagonists (zafirlukast [Accolate], montelukast [Singulair] and pranlukast) and one 5-lipoxygenase inhibitor (zileuton) have received regulatory approval for the treatment of asthma. The clinical data obtained from using these drugs are generally consistent and complimentary. As a class the leukotriene modulators produce a rapid improvement in lung function after the first oral dose. Lung function improvements are maintained on chronic administration and are associated with reductions in a variety of asthma symptom scores. All of the available data are consistent with the hypothesis that all the leukotriene modulators exert their clinical benefit primarily through interference with cysteinyl leukotrienes. There are no compelling clinical data for an additional contribution by leukotriene B(4)in human asthma. In other respiratory conditions such as COPD, which are characterised by pronounced neutrophil infiltration, it may be that the chemotactic properties of leukotriene B(4)are more important and therefore evaluation of 5-lipoxygenase inhibitors in this condition is warranted. The introduction of the leukotriene modulators into clinical practice is the culmination of over 60 years of research since the initial discovery of the slow-reacting substances. The leukotriene modulators, and in particular the cysteinyl leukotriene antagonists, provide respiratory physicians with an oral therapeutic option and have set an efficacy standard which new oral anti-inflammatory approaches will have to beat.

Authors+Show Affiliations

AstraZeneca, Mereside, Alderley Park, Macclesfield, SK, 10 4TG, UK.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

12052325

Citation

McMillan, R M.. "Leukotrienes in Respiratory Disease." Paediatric Respiratory Reviews, vol. 2, no. 3, 2001, pp. 238-44.
McMillan RM. Leukotrienes in respiratory disease. Paediatr Respir Rev. 2001;2(3):238-44.
McMillan, R. M. (2001). Leukotrienes in respiratory disease. Paediatric Respiratory Reviews, 2(3), 238-44.
McMillan RM. Leukotrienes in Respiratory Disease. Paediatr Respir Rev. 2001;2(3):238-44. PubMed PMID: 12052325.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leukotrienes in respiratory disease. A1 - McMillan,R M, PY - 2002/6/8/pubmed PY - 2002/6/26/medline PY - 2002/6/8/entrez SP - 238 EP - 44 JF - Paediatric respiratory reviews JO - Paediatr Respir Rev VL - 2 IS - 3 N2 - Arachidonic acid metabolism via 5-lipoxygenase gives rise to a group of biologically active lipids known as leukotrienes: leukotriene B(4), which is a potent activator of leukocyte chemotaxis, and cysteinyl leukotrienes (leukotriene C(4), D(4)and E(4)) which account for the spasmogenic activity previously described as slow-reacting substance of anaphylaxis. The biological actions of leukotrienes and the observations that leukotrienes are synthesised in the lung following antigen provocation and are elevated in asthma, stimulated considerable activity in the pharmaceutical industry to find drugs that modulate the synthesis or actions of leukotrienes. Three cysteinyl leukotriene antagonists (zafirlukast [Accolate], montelukast [Singulair] and pranlukast) and one 5-lipoxygenase inhibitor (zileuton) have received regulatory approval for the treatment of asthma. The clinical data obtained from using these drugs are generally consistent and complimentary. As a class the leukotriene modulators produce a rapid improvement in lung function after the first oral dose. Lung function improvements are maintained on chronic administration and are associated with reductions in a variety of asthma symptom scores. All of the available data are consistent with the hypothesis that all the leukotriene modulators exert their clinical benefit primarily through interference with cysteinyl leukotrienes. There are no compelling clinical data for an additional contribution by leukotriene B(4)in human asthma. In other respiratory conditions such as COPD, which are characterised by pronounced neutrophil infiltration, it may be that the chemotactic properties of leukotriene B(4)are more important and therefore evaluation of 5-lipoxygenase inhibitors in this condition is warranted. The introduction of the leukotriene modulators into clinical practice is the culmination of over 60 years of research since the initial discovery of the slow-reacting substances. The leukotriene modulators, and in particular the cysteinyl leukotriene antagonists, provide respiratory physicians with an oral therapeutic option and have set an efficacy standard which new oral anti-inflammatory approaches will have to beat. SN - 1526-0542 UR - https://www.unboundmedicine.com/medline/citation/12052325/Leukotrienes_in_respiratory_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-0542(01)90146-0 DB - PRIME DP - Unbound Medicine ER -