Fibrosis is a common end-stage sequella of a number of acute and chronic
lung diseases. Current concepts of pathogenesis implicate dysregulated interactions between epithelial cells and mesenchymal cells. Although investigative efforts have documented important roles for
cytokines and
growth factors in the pathogenesis of fibrotic
lung diseases, these observations have not as yet been translated into efficacious
therapies, and there is a pressing need for new pathogenetic insights and therapeutic approaches for these devastating disorders.
Eicosanoids are
lipid mediators derived from
arachidonic acid, the most studied of which are the
prostaglandins and
leukotrienes. Although they are primarily known for their roles in
asthma,
pain,
fever and vascular responses, present evidence indicates that
eicosanoids exert relevant effects on immune/inflammatory, as well as structural, cells pertinent to fibrogenesis. In general,
leukotrienes promote, whereas
prostaglandin E(2) opposes, fibrogenic responses. An imbalance of
eicosanoids also exists in
pulmonary fibrosis, which favours the production of
leukotrienes over
prostaglandin E(2). This review highlights the role of this imbalance in the evolution of fibrotic
lung disease, discusses the mechanisms by which it may arise and considers approaches for therapeutic targeting of
eicosanoids in these conditions.