title: Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease--a randomized placebo-controlled study.
abstract: The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, C-reactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth factor (TGF)-beta1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months (P=0.04 and P<0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P<0.01) with a trend towards a higher increase of TGF-beta1 in the former group (P=0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events.
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Brazil. Electronic address: jlaraf@terra.com.br.
authors.forename: Juliano Lara
authors.initials: JL
authors.lastname: Fernandes
authors.affiliation: State University of Campinas (UNICAMP), Brazil.
authors.forename: Romulo Tadeu Dias
authors.initials: RTD
authors.lastname: de Oliveira
authors.affiliation: State University of Campinas (UNICAMP), Brazil.
authors.forename: Ronei Luciano
authors.initials: RL
authors.lastname: Mamoni
authors.affiliation: State University of Campinas (UNICAMP), Brazil.
authors.forename: Otavio Rizzi
authors.initials: OR
authors.lastname: Coelho
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Brazil.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Nicolau
authors.affiliation: State University of Campinas (UNICAMP), Brazil.
authors.forename: Maria Heloisa S L
authors.initials: MHSL
authors.lastname: Blotta
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Brazil.
authors.forename: Carlos Vicente
authors.initials: CV
authors.lastname: Serrano
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007371:Interferon-gamma / Q000187:drug effects; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D007378:Interleukins; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002097:C-Reactive Protein; D010431:Pentoxifylline