Extending the understanding of leukotrienes in asthma.
OBJECTIVE
Leukotriene modifiers have recognized utility in the management of asthma. The aim of this review is to put into context recent research findings that extend our understanding of cysteinyl leukotriene synthesis and actions in the pathogenesis of asthma and allergic disease.


RESULTS
Previous literature has shown that T helper type 2 cytokines thought to favor asthma and allergic diseases upregulate leukotriene synthesis. Recent findings show that interleukins-4 and -13 also upregulate cysteinyl leukotriene 1 receptor expression. Conversely, the regulation of cytokine expression by leukotrienes has also been explored: cysteinyl leukotrienes upregulate type 2 cytokine expression and decrease type 1 cytokine expression, favoring an allergic phenotype. Genetic determinants of the expression of leukotriene-forming enzymes include polymorphisms of the 5-lipoxygenase and LTC(4) synthase promoters. Novel actions of leukotrienes continue to be recognized, and a role for leukotrienes in the development of airway remodeling accompanying chronic asthma is discussed. Mounting evidence implicates leukotrienes in the pathogenesis of asthma following viral infections. Finally, advances in the measurement of leukotrienes are reviewed.


CONCLUSIONS
Leukotrienes and their receptors play an important role in the pathogenesis of asthma. Advances in our understanding of the synthesis and actions of these lipid mediators provide the scientific rationale for appropriate utilization of leukotriene modifiers and for envisioning novel leukotriene-based therapeutic approaches in the clinical management of asthma.
Coffey
Michael
M
University of Michigan Health System, Ann Arbor, USA.
Peters-Golden
Marc
M
D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D002648:Child; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D008565:Membrane Proteins; D011110:Polymorphism, Genetic; D018077:Receptors, Leukotriene / Q000378:metabolism
D015289:Leukotrienes; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C412375:cysteinyl leukotriene receptor 2; D001094:Arachidonate 5-Lipoxygenase; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C083169:leukotriene D4 receptor