Eicosanoids are a group of lipid mediators derived from the 20-carbon fatty acid arachidonic acid (eicosa is Greek for “20”). After release from membrane phospholipids by cytosolic phospholipase A2 (Fig 1
), arachidonate is further metabolized by the 5-lipoxygenase (5-LO) pathway into LTs or by the cyclooxygenase (COX)-1/COX-2 pathway into PGs.3LTs include both LTB4 and the cysteinyl LTs (cysLTs) C4, D4, and E4, and are synthesized mainly by leukocytes. PGs, including PGE2, PGI2, PGD2, PGF2α, and thromboxane A2, are synthesized by both leukocytes and structural cells. Individual cell types generate specific profiles of eicosanoids that reflect their complement of terminal synthase enzymes. LTs and PGs exert a myriad of actions that contribute to both homeostasis and disease. Eicosanoids act in a paracrine or autocrine fashion by ligating specific 7-transmembrane G protein-coupled receptors. These receptors signal via changes in intracellular cyclic adenosine monophosphate (cAMP), calcium, or diacylglycerol, depending on the type of associated G protein. Though best known for their role in pain, fever, and inflammatory disorders such as asthma and arthritis, a substantial body of research4 has shown that they modulate pulmonary fibroproliferative responses as well. Eicosanoids can affect the fibroproliferative response both directly, via actions on structural cells, and indirectly, by modulating inflammatory cells, mediators, and other pathways that are important in pulmonary fibrosis.