Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease--a randomized placebo-controlled study.
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.
Fernandes
Juliano Lara
JL
Heart Institute (InCor), University of Sao Paulo Medical School, Brazil. Electronic address: jlaraf@terra.com.br.
de Oliveira
Romulo Tadeu Dias
RTD
State University of Campinas (UNICAMP), Brazil.
Mamoni
Ronei Luciano
RL
State University of Campinas (UNICAMP), Brazil.
Coelho
Otavio Rizzi
OR
State University of Campinas (UNICAMP), Brazil.
Nicolau
Jose Carlos
JC
Heart Institute (InCor), University of Sao Paulo Medical School, Brazil.
Blotta
Maria Heloisa S L
MHSL
State University of Campinas (UNICAMP), Brazil.
Serrano
Carlos Vicente
CV
Heart Institute (InCor), University of Sao Paulo Medical School, Brazil.
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
D007378:Interleukins; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002097:C-Reactive Protein; D010431:Pentoxifylline