Artículos de revistas
Pentoxifylline Reduces Pro-inflammatory And Increases Anti-inflammatory Activity In Patients With Coronary Artery Disease-a Randomized Placebo-controlled Study
Atherosclerosis. , v. 196, n. 1, p. 434 - 442, 2008.
de Oliveira R.T.D.
Serrano Jr. C.V.
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 400 mg 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)-α and the anti-inflammatory cytokines, transforming growth factor (TGF)-β1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-α 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-β1 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. © 2006 Elsevier Ireland Ltd. All rights reserved.1961434442Hansson, G.K., Inflammation, atherosclerosis, and coronary artery disease (2005) N Engl J Med, 352, pp. 1685-1695Frostegard, J., Ulfgren, A.K., Nyberg, P., Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines (1999) Atherosclerosis, 145, pp. 33-43Zhou, X., Paulsson, G., Stemme, S., Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice (1998) J Clin Invest, 101, pp. 1717-1725Uyemura, K., Demer, L.L., Castle, S.C., Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis (1996) J Clin Invest, 97, pp. 2130-2138Fernandes, J.L., Mamoni, R.L., Orford, J.L., Increased Th1 activity in patients with coronary artery disease (2004) Cytokine, 26, pp. 131-137Liuzzo, G., Vallejo, A.N., Kopecky, S.L., Molecular fingerprint of interferon-gamma signaling in unstable angina (2001) Circulation, 103, pp. 1509-1514Liuzzo, G., Biasucci, L.M., Gallimore, J.R., The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina (1994) N Engl J Med, 331, pp. 417-424Biasucci, L.M., Vitelli, A., Liuzzo, G., Elevated levels of interleukin-6 in unstable angina (1996) Circulation, 94, pp. 874-877Pinderski Oslund, L.J., Hedrick, C.C., Olvera, T., Interleukin-10 blocks atherosclerotic events in vitro and in vivo (1999) Arterioscler Thromb Vasc Biol, 19, pp. 2847-2853Grainger, D.J., Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis (2004) Arterioscler Thromb Vasc Biol, 24, pp. 399-404Cipollone, F., Fazia, M., Mincione, G., Increased expression of transforming growth factor-beta1 as a stabilizing factor in human atherosclerotic plaques (2004) Stroke, 35, pp. 2253-2257Mallat, Z., Tedgui, A., The role of transforming growth factor beta in atherosclerosis: novel insights and future perspectives (2002) Curr Opin Lipidol, 13, pp. 523-529Lutgens, E., Cleutjens, K.B., Heeneman, S., Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype (2000) Proc Natl Acad Sci USA, 97, pp. 7464-7469Zhao, L., Cuff, C.A., Moss, E., Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemia (2002) J Biol Chem, 277, pp. 35350-35356Laurat, E., Poirier, B., Tupin, E., In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice (2001) Circulation, 104, pp. 197-202Ramani, M., Khechai, F., Ollivier, V., Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes (1994) FEBS Lett, 356, pp. 86-88D'Hellencourt, C.L., Diaw, L., Cornillet, P., Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline (1996) Int J Immunopharmacol, 18, pp. 739-748Ward, A., Clissold, S.P., Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy (1987) Drugs, 34, pp. 50-97Sliwa, K., Woodiwiss, A., Kone, V.N., Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study (2004) Circulation, 109, pp. 750-755Ridker, P.M., Cannon, C.P., Morrow, D., C-reactive protein levels and outcomes after statin therapy (2005) N Engl J Med, 352, pp. 20-28Bhatt, D.L., Topol, E.J., Need to test the arterial inflammation hypothesis (2002) Circulation, 106, pp. 136-140Belloc, F., Jaloustre, C., Dumain, P., Effect of pentoxifylline on apoptosis of cultured cells (1995) J Cardiovasc Pharmacol, 25 (SUPPL. 2), pp. S71-S74Neuner, P., Klosner, G., Schauer, E., Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells (1994) Immunology, 83, pp. 262-267Boldt, J., Brosch, C., Lehmann, A., Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery patients (2001) Ann Thorac Surg, 71, pp. 1524-1529Boldt, J., Brosch, C., Piper, S.N., Influence of prophylactic use of pentoxifylline on postoperative organ function in elderly cardiac surgery patients (2001) Crit Care Med, 29, pp. 952-958Benagiano, M., Azzurri, A., Ciervo, A., T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions (2003) Proc Natl Acad Sci USA, 100, pp. 6658-6663Gupta, S., Pablo, A.M., Jiang, X., IFN-gamma potentiates atherosclerosis in ApoE knock-out mice (1997) J Clin Invest, 99, pp. 2752-2761Terkeltaub, R.A., IL-10: an "immunologic scalpel" for atherosclerosis? (1999) Arterioscler Thromb Vasc Biol, 19, pp. 2823-2825Heeschen, C., Dimmeler, S., Hamm, C.W., Serum level of the antiinflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes (2003) Circulation, 107, pp. 2109-2114Bogaty, P., Brophy, J.M., Noel, M., Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study (2004) Circulation, 110, pp. 934-939