title: Lovastatin dose-dependently potentiates the pro-inflammatory activity of lipopolysaccharide both in vitro and in vivo.
abstract: Since contradictory findings have been reported on potential effects of statins in modulating the inflammatory response, we have analysed the biological activity of lovastatin both in vitro using the Raw 264.7 murine macrophagic cell line and in vivo using BALB/c mice. When added to Raw 264.7 cells in combination with lipopolysaccharide, lovastatin significantly potentiated the release of interleukin-1β, interleukin-6 and interleukin-12 with respect to lipopolysaccharide alone and showed an additive effect on the release of nitric oxide. Similarly, when lovastatin was intraperitoneally administrated to BALB/c mice, it did not induce any pro-inflammatory effect when used alone, but it significantly potentiated the pro-inflammatory activity of lipopolysaccharide, in terms of number of intraperitoneal cells and serum levels of serum amyloid A, interleukin-1β, interleukin-6 and interleukin-12. A potential clinical implication of our study is that lovastatin might exert a pro-inflammatory activity in subjects affected by inflammatory processes, with clinically evident or subclinical infections.
authors: Valentina
authors: V
authors: Zanin
authors: Annalisa
authors: A
authors: Marcuzzi
authors: Giulio
authors: G
authors: Kleiner
authors: Elisa
authors: E
authors: Piscianz
authors: Lorenzo
authors: L
authors: Monasta
authors: Serena
authors: S
authors: Zacchigna
authors: Sergio
authors: S
authors: Crovella
authors: Giorgio
authors: G
authors: Zauli
mesh_terms: D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000685:Serum Amyloid A Protein; C577686:interleukin-6, mouse; C482199:lipopolysaccharide, E coli O55-B5; D018664:Interleukin-12; D009569:Nitric Oxide; D002784:Cholesterol
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