Arachidonic acid metabolism in fibroblasts from patients with peroxisomal diseases: response to interleukin 1

E₂ synthesis and eicosanoid biosynthetic enzyme activities (arachidonyl CoA synthetase, cyclooxygenase and phospholipase A₂) were measured in dermal fibroblasts from patients with metablic disorders of peroxisomal origin and compared to those from normal subjects and patients with other metabolic disorders of lipid metabolism. Basal- as well as interleukin 1-stimulated prostaglandin E₂ syntheses were higher in fibroblasts from patients with X-linked adrenoleukodystrophy, the Zellweger cerebrohepatorenal syndrome and rhizomelic chondrodysplasia punctata than in normals. Basal cyclooxygenase and phospholipase A₂ activities were elevated in most of the peroxisomal disease cells. Cells from patients with adrenomyeloneuropathy, however, had significantly lower cytokine-stimulated cyclooxygenase and phospholipase A₂ activities that normals, as well as lower prostaglandin E₂ synthesis in response to interleukin 1. The peroxisomal disease lines exhibited dose-response curves to interleukin 1 similar to controls. Receptor-binding analysis indicated that cells from patients with rhizomelic chondrodysplasia punctata expressed 5-times fewer interleukin 1 receptors than normals and the other disease lines. Exaggerated arachidonic acid metabolism in response to interleukin 1 suggests that cells from patients with peroxisomal enzyme defects may be useful in elucidating pathways for arachidonate release and eicosanoid synthesis.