title: Niacin Modulates Pro-inflammatory Cytokine Secretion. A Potential Mechanism Involved in its Anti-atherosclerotic Effect.
abstract: The pathogenesis of atherosclerosis includes the assignment of a critical role to cells of the monocyte/macrophage lineage and to pro-inflammatory cytokines. Niacin is known to improve lipid metabolism and to produce beneficial modification of cardiovascular risk factors. The aim of this work was to investigate if Niacin is able to modulate pro-inflammatory cytokine production in macrophages in a murine model of atherosclerosis. For this purpose C57Bl/6J mice fed with atherogenic diet (AGD) or with conventional chow diet were used. The AGD group showed an increase in body weight and in total plasma cholesterol, with no differences in triglyceride or HDL levels. Lesions in arterial walls were observed. The characterization of Niacin receptor showed an increase in the receptor number of macrophages from the AGD group. Macrophages from control and AGD animals treated in vitro with an inflammatory stimulus showed elevated levels of IL-6, IL-1 and TNF-α, that were even higher in macrophages from AGD mice. Niacin was able to decrease the production of pro-inflammatory cytokines in stimulated macrophages. Similar effect of Niacin was observed in an in vivo model of inflammation. These results show an attenuating inflammatory mechanism for this therapeutic agent and would point out its potential action in plaque stabilization and in the prevention of atherosclerosis progression. Furthermore, the present results provide the basis for future studies on the potential contribution of Niacin to anti-inflammatory therapies.
authors.affiliation: Primera Cátedra de Farmacología, Departamento de Farmacología Facultad de Medicina, Universidad de Buenos Aires (UBA), Argentina.
authors.forename: Pedro Saul
authors.initials: PS
authors.lastname: Lipszyc
authors.forename: Graciela Alicia
authors.initials: GA
authors.lastname: Cremaschi
authors.forename: María
authors.initials: M
authors.lastname: Zorrilla-Zubilete
authors.forename: Maria Laura Aón
authors.initials: ML
authors.lastname: Bertolino
authors.forename: Francisco
authors.initials: F
authors.lastname: Capani
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Genaro
authors.forename: Miriam Ruth
authors.initials: MR
authors.lastname: Wald
keywords: Niacin; atherosclerosis; inflammation; macrophages; nicotinic acid receptor; pro-inflammatory cytokine.