title: Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush.
abstract: Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D2 (PGD2) mediated niacin flush. Previous research suggests that nicotinic acid-induced PGD2 secretion is mediated by the skin, but the exact cell type remains unclear. We hypothesized that macrophages are a source of nicotinic acid-induced PGD2 secretion and performed a series of experiments to confirm this. Nicotinic acid (0.1-3 mM) induced PGD2 secretion in cultured human macrophages, but not monocytes or endothelial cells. The PGD2 secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD2 secretion. Pre-incubation of the cells with aspirin (100 microM) entirely prevented the nicotinic acid effects on PGD2 secretion. The PGD2 secreting effects of nicotinic acid were additive to the effects of the calcium ionophore A23187 (6 microM), but were independent of extra cellular calcium. These findings, combined with recent in vivo work, provide evidence that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect.
authors.affiliation: Long Beach Veterans Affairs Healthcare System, Long Beach, CA, United States. dan.meyers@novartis.com <dan.meyers@novartis.com>
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Meyers
authors.forename: Paul
authors.initials: P
authors.lastname: Liu
authors.forename: Vaijinath S
authors.initials: VS
authors.lastname: Kamanna
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005483:Flushing / Q000139:chemically induced*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D009525:Niacin / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009539:Nicotinic Acids / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D009539:Nicotinic Acids; D009525:Niacin; D000001:Calcimycin; C002477:nicotinuric acid; D001241:Aspirin; D015230:Prostaglandin D2; D002118:Calcium