title: Beneficial Effects of Pentoxifylline in Patients With Idiopathic Dilated Cardiomyopathy Treated With Angiotensin-Converting Enzyme Inhibitors and Carvedilol: Results of a Randomized Study C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial. Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline: Results of a Randomized Study Pentoxifylline, Inflammation, and Endothelial Function in HIV-Infected Persons: A Randomized, Placebo-Controlled Trial The effect of pentoxifylline on reduction of proteinuria among patients with type 2 diabetes under blockade of angiotensin system: a double blind and randomized clinical trial. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Effect of Pentoxifylline on Microalbuminuria in Diabetic Patients: A Randomized Controlled Trial Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease--a randomized placebo-controlled study. OXPENTIFYLLINE IN ENDOTOXAEMIA Effect of Pentoxifylline on inflammatory burden, oxidative stress and platelet aggregability in hypertensive type 2 diabetes mellitus patients. Effects of pentoxifylline on the cytokines that may play a role in rejection and resistive index in renal transplant recipients. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial.
abstract: Background —We previously reported beneficial effects of pentoxifylline , a xanthine-derived agent known to inhibit the production of tumor necrosis factor-&agr ; , in patients with idiopathic dilated cardiomyopathy treated with diuretics , digoxin , and ACE inhibitors .  Since then , 3 large clinical trials showed important clinical benefits of & bgr;-blockers in this population . Therefore , we design ed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and & bgr;-blockers , the addition of pentoxifylline would have an additive beneficial effect . Methods and Results —In a single-center , prospect i ve , double-blind , r and omized , placebo-controlled study , 39 patients with idiopathic dilated cardiomyopathy were r and omized to pentoxifylline 400 mg TID ( n=20 ) or placebo ( n=19 ) if they had a left ventricular ejection fraction < 40 % after 3 months of therapy with digoxin , ACE inhibitors , and carvedilol . Primary end points were New York Heart Association functional class , exercise tolerance , and left ventricular function . Patients were followed up for 6 months . Five patients died ( 3 in the placebo group ) . Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group ( P = 0.01 ) , with an increment in exercise time from 9.5±5 to 12.3±6 minutes ( P = 0.1 ) . Left ventricular ejection fraction improved from 24±9 % to 31±13 % , P = 0.03 , in the treatment group . Conclusions —In patients with idiopathic dilated cardiomyopathy , the addition of pentoxifylline to treatment with digoxin , ACE inhibitors , and carvedilol is associated with a significant improvement in symptoms and left ventricular function BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy ( DN ) , albuminuria and progression of renal disease are not completely halted by these agents . Therefore , it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches . This study tested the hypothesis that the combination of pentoxifylline ( PTF ) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect .  Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for > 1 yr were r and omly assigned to receive the addition of 1200 mg of PTF daily ( n = 30 ) or to a control group ( n = 31 ) . Baseline characteristics were similar between groups , and correlation analysis showed a significant association between urinary albumin excretion ( UAE ) and urinary TNF-alpha ( R = 0.53 , P < 0.001 ) . After 4 mo , albuminuria showed a significant decrease in patients who received PTF , from 900 mg/24 h ( 466 to 1542 mg/d ) to 791 mg/24 h ( 309 to 1400 mg/d ; P < 0.001 ) , whereas no significant changes were observed in the control group : 920 mg/24 h ( 450 to 1489 mg/d ) at baseline , and 900 mg/24 h ( 428 to 1800 mg/d ) at the end of the study . The mean percentage variation of UAE in the treatment and control groups was -16.7 and 5.5 % , respectively ( between-group comparison , P < 0.001 ) . This additive antiproteinuric effect was not dependent on changes in BP or metabolic control . However , both serum and urinary levels of TNF-alpha also decreased in patients who received PTF , from 6.4 pg/ml ( 2.1 to 9.7 ) and 16 pg/mg ( 8 to 29 ) at baseline to 4.6 pg/ml ( 0.4 to 9 ) and 14.2 pg/mg ( 3 to 26 ) at the end of the study , respectively ( P < 0.01 ) , without significant variations in control patients . Moreover , regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-alpha in patients who were treated with PTF ( R = 0.49 , P < 0.001 ) . In conclusion , administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-alpha excretion Background —Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome . We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy . We also investigated the effect of therapy on levels of brain natriuretic peptide ( NT-pro BNP ) , C-reactive protein ( CRP ) , tumor necrosis factor-&agr ; ( TNF-&agr ; ) , and the marker of apoptosis , Fas/Apo-1 . Methods and Results —In a single-center , prospect i ve , r and omized , double-blind , placebo-controlled  study , 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to st and ard therapy .  Clinical assessment , radionuclide ventriculography , echocardiography , and blood analyses were performed at baseline and after 6 months . There were no differences in baseline characteristics between the groups . Five patients died  ( 4 in the placebo group ) . Pentoxifylline treatment result ed in an improvement in functional class ( P < 0.005 ) and an increase in systolic blood pressure ( P < 0.05 ) and left ventricular radionuclide ejection fraction ( P < 0.05 ) compared with the placebo-treated group . There were reductions in plasma concentrations of CRP , NT-pro BNP , TNF-&agr ; , and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group . Conclusions —In patients with heart failure due to ischemic left ventricular dysfunction , the addition of pentoxifylline to st and ard therapy results in improvements in clinical status and radionuclide ejection fraction , which are accompanied by reductions in plasma markers of inflammation , prognosis , and apoptosis Background Untreated HIV may increase the risk of cardiovascular events . Our preliminary in vitro and in vivo research suggests that pentoxifylline ( PTX ) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy . Methods We performed a r and omized , placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants . The primary endpoint was change in flow-mediated dilation ( FMD ) of the brachial artery after 8 weeks . Nitroglycerin-mediated dilation ( NTGMD ) and circulating markers of inflammation , cellular immune activation , coagulation , and metabolism were also assessed . Results The difference in mean absolute change ( SD ) in FMD after 8 weeks between the placebo [ −1.06 (1.45)% ] and PTX [ −1.93 (3.03)% ] groups was not significant ( P = 0.44 ) . No differences in NTGMD were observed . The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 ( sTNFRI ) [ −83.2 pg/mL in the placebo group vs. + 65.9 pg/mL in the PTX group ; P = 0.03 ] . PTX was generally well-tolerated . Conclusions PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy . Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population . Trial Registration Clinical Trials.gov Although blockade of renin-angiotensin system have been cited as the first line of therapy for the management of diabetic nephropathy ( DN ) , however in a substantial number of patients , progression of renal disease are not completely halted by these agents . We have conducted a double blinded clinical trial to assess the additive effect of pentoxifylline on reduction of proteinuria among patients with type 2 DM under blockade of angiotensin system . The dosage of PTX used in our trial was at a low dosage of 400 mg daily and to our knowledge , we did not found article which evaluated the antiproteinuric effect of pentoxifylline in this dosage . One hundred patients with DN and persistent proteinuria despite treatment with losartan and enalapril in at least 3 months before inclusion in the study were r and omly assigned to two groups . Control group ( n=50 , 26 males and 24 females ) received losartan and enalapril , while treatment group ( PTX Group ) ( n=50 , 28 males and 22 females ) was given losartan , enalapril and pentoxifylline 400mg/day for 6 months . At the beginning of the study there were no significant differences in demographic and clinical characteristics of patients including serum creatinine , HbA1c , blood pressure and urinary protein excretion between two groups ( P>.05 ) . In the PTX group , the mean rate of urinary protein excretion have significantly decreased from 616.66 mg to 378.24 after 3 months ( P=.000 ) and to 192.05 mg after 6 months ( P=.000 ) whereas no significant changes were observed in the control group . The beneficial antiproteinuric effect of PTX was not associated to the degree of metabolic control and a reduction of blood pressure . In addition , at the end of study , the mean clearance of creatinine was significantly higher in PTX group ( P=.04 ) . In conclusion , PTX can significantly provide additive antiproteinuric effect and slow the decrease in GFR among patients with type 2 DM under blockade of angiotensin system INTRODUCTION The burden of non-alcoholic steatohepatitis ( NASH ) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy . Pilot studies suggest that pentoxifylline ( PTX ) can reduce liver injury in patients with NASH . OBJECTIVE We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH . MATERIAL AND METHODS Thirty patients with biopsy proven NASH were r and omized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months . Metabolic parameters , aminotransferases , liver histology and hepatic gene expression changes were compared . RESULTS At baseline the groups were similar . Adverse events were mild , most frequently headache and abdominal cramps , and did not differ between groups ( p = NS ) . After 12 months , ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L ( p < 0.05 ) , respectively in patients treated with PTX . No significant effect was seen with  placebo . Steatosis and cellular ballooning improved in the PTX group ( p < 0.05 ) , whereas no histological feature of steatohepatitis improved with placebo . However , between groups comparison of both biochemical and histological features were nonsignificant . CONCLUSION Pentoxifylline is safe , well tolerated and improves transaminases and histology in patients with NASH when compared to baseline and may be a reasonable therapeutic modality for the treatment of NASH . However PTX failed to reduce transaminases compared to placebo and did not positively affect any of the metabolic markers postulated to contribute to NASH . Although animal data and small pilot studies in humans have suggested that PTX may be effective as a treatment for NASH , translating this therapy to clinical practice may prove challenging Background . Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties . Human studies have proved its antiproteinuric effect in patients with glomerular diseases , but this study was design ed to assess the effects of add-on pentoxifylline to available treatment on reduction of microalbuminuria in diabetic patients without glomerular diseases . Methods . In a double-blind placebo-controlled , r and omized study we evaluated the influence of pentoxifylline on microalbuminuria in type 2 diabetic patients . 40 diabetic patients with estimated glomerular filtration rate ( eGFR ) of more than 60 mL/min/1.73 m2 in eight weeks and microalbuminuria were r and omized to two groups which will receive pentoxifylline 1200 mg/day or placebo added to regular medications for 6 months . albuminuria ; eGFR was evaluated at three- and six-month follow-up period . Results . Baseline characteristics were similar between the two groups . At six months , the mean estimated GFR and albuminuria were not different between two groups at 3- and 6-month follow-up . Trend of albumin to creatinine ratio , systolic and diastolic blood pressure , and eGFR in both groups were decreased , but no significant differences were noted between two groups ( P value > 0.05 ) . Conclusion . Pentoxifylline has not a significant additive antimicroalbuminuric effect compared with placebo in patients with type 2 diabetes with early stage of kidney disease ; however , further clinical investigations are necessary to be done Abstract Background Non-alcoholic fatty liver disease is a common health problem associated with increased liver and vascular specific complications . Aim The purpose of this study was to assess and compare the effect of fenofibrate alone or in combination with pentoxifylline on the measured biochemical parameters , inflammatory pathway and liver stiffness in patients with non-alcoholic fatty liver disease . Methods The study design was r and omized controlled trial . From July 2013 to June 2014 , we recruited 90 non-alcoholic fatty liver patients from the Internal Medicine Department at Tanta University Hospital , Egypt . They were classified r and omly into two groups to receive fenofibrate 300 mg daily or fenofibrate 300 mg daily plus pentoxifylline 1200 mg/day in three divided doses for 24 weeks . Fasting blood sample was obtained before and 24 weeks after treatment for biochemical analysis of liver and lipid panels , tumor necrosis factor-alpha , hyaluronic acid , transforming growth factor beta 1 , fasting plasma insulin and fasting glucose . Liver stiffness measurement was carried out using fibro-scan . Data were statistically analyzed by paired and unpaired Student ’s t test . Results The data obtained suggests that adding pentoxifylline to fenofibrate does not provide a beneficial effect on lipid panel , but has a beneficial effect on indirect biochemical markers of hepatic fibrosis , a direct marker linked to matrix deposition ( hyaluronic acid ) , a cytokine/growth factor linked to liver fibrosis ( transforming growth factor beta 1 ) , the inflammatory pathway , insulin resistance and liver stiffness as compared to fenofibrate alone . Conclusion The combination pentoxifylline plus fenofibrate may represent a new therapeutic strategy for non-alcoholic fatty liver disease as it result ed in more beneficial effects on direct and indirect markers of liver fibrosis , liver stiffness , insulin resistance and inflammatory pathway implicated in NAFLD BACKGROUND There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure . Plasma concentrations of tumour necrosis factor alpha ( TNF-alpha ) are high in heart failure and have been correlated with the severity of symptoms . Pentoxifylline suppresses the production of TNF-alpha . This study aim ed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy . METHODS We undertook a single-centre , prospect i ve , double-blind , r and omised , placebo-controlled trial , in which 28 patients with idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times daily or matching placebo .  Clinical , echocardiographic , and radionuclide assessment s were done at baseline and after 6 months of treatment . Primary endpoints were New York Heart Association ( NYHA ) functional class and left-ventricular function . FINDINGS Baseline characteristics were similar in the two groups . Four patients  died during the study period , all in the placebo group . After 6 months of treatment , the proportion of patients in NYHA functional class I or II was higher in the pentoxifylline group than in the placebo group ( 14/14 vs 10/14 ; p=0.01 ) , and ejection fraction was higher in the pentoxifylline group than in the placebo group ( mean 38.7 % [ SD 15.0 ] vs 26.8 % [ 11.0 ] , p=0.04 ) . At 6 months , TNF-alpha plasma concentrations were significantly lower in the pentoxifylline-treated group than in the placebo group ( 2.1 [ 1.0 ] vs 6.5 [ 5.0 ] pg/mL , p=0.001 ) . INTERPRETATION Our results suggest that pentoxifylline improves symptoms and left-ventricular systolic function in patients with idiopathic dilated cardiomyopathy . These results must be confirmed in larger-scale trials INTRODUCTION Tumor necrosis factor (TNF)-alpha and interleukin-6 ( IL-6 ) are significantly elevated in patients with congestive heart failure ( CHF ) .  Pentoxifylline , a xanthin-derived agent , is known to inhibit the production of TNF-alpha and IL-6 . Recent studies have shown that pentoxifylline produces an increase in ejection fraction , a decrease in left-ventricular chamber size and an improvement in clinical status in patients with idiopathic-dilated cardiomyopathy . Therefore , we studied the effects of pentoxifylline in ischemic , hypertensive and idiopathic-dilated cardiomyopathy . METHODS Primary endpoint was left-ventricular ejection fraction ( LVEF ) assessed by contrast 2D echocardiography . Secondary endpoints were concentrations of TNF-alpha , IL-6 , brain natriuretic peptide , maximal oxygen uptake ( VO(2 max ) ) assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Question naire score or New York Heart Association scale . RESULTS Forty-seven patients ( 31.9 % ischemic , 21.3 % hypertensive , 10.6 % ischemic and hypertensive , 36.2 % idiopathic-dilated cardiomyopathy ) were r and omly assigned to pentoxifylline 600 mg BID ( n=23 ) or placebo ( n=24 ) if they had a compensated CHF with a LVEF less than or equal to 40 % and had taken their st and ard treatment consisting of angiotensin-converting enzyme inhibitors , diuretics and beta-blockers for at least 3 months . Baseline demographic and clinical characteristics of each group were similar . Forty-one patients completed the study protocol and were analysed for primary and secondary endpoints . After 6 months of treatment , LVEF was unchanged in the pentoxifylline group compared with placebo ( 29+/-7 to 33+/-10 % vs. 27+/-9 to 34+/-9 % , respectively , P = NS ) . Also the secondary endpoints did not significantly change during follow-up . CONCLUSION Additional treatment with pentoxifylline is neutral with regard to left-ventricular function , inflammatory cytokines and symptoms in patients with ischemic , hypertensive and idiopathic-dilated cardiomyopathy UNLABELLED The primary aim of this study was to compare the effects of pentoxifylline ( PTX ) versus placebo on the histological features of nonalcoholic steatohepatitis ( NASH ) . In all , 55 adults with biopsy-confirmed NASH were r and omized to receive PTX at a dose of 400 mg three times a day ( n = 26 ) or placebo ( n = 29 ) over 1 year . The primary efficacy endpoint was defined as improvement in histological features of NASH through reduction in steatosis , lobular inflammation , and /or hepatocellular ballooning as reflected by a decrease of ≥ 2 points in the nonalcoholic fatty liver disease ( NAFLD ) activity score ( NAS ) . After 1 year , intention-to-treat analysis showed a decrease of ≥ 2 points in the NAS in 38.5 % of patients on PTX versus 13.8 % of those on placebo ( P = 0.036 ) . Per protocol analysis , a decrease of ≥ 2 points in the NAS from baseline was observed in 50 % of the patients on PTX versus 15.4 % of those on placebo ( P = 0.01 ) . The mean change in NAS score from baseline was -1.6 in the PTX group , versus -0.1 in the placebo group ( P < 0.001 ) . PTX  significantly improved steatosis ( mean change in score -0.9 versus -0.04 with placebo , P < 0.001 ) and lobular inflammation ( median change -1 versus 0 with placebo , P = 0.02 ) . No significant effects in hepatocellular ballooning were observed . PTX  also improved liver fibrosis ( mean change in fibrosis score was -0.2 among those on PTX versus + 0.4 among those on placebo , P = 0.038 ) . Although not statistically significant ( P = 0.17 ) , improvement in fibrosis was observed in a greater proportion ( 35 % ) of patients in the PTX group compared to placebo ( 15 % ) . Adverse effects were similar in both groups . CONCLUSION PTX  improved histological features of NASH compared to placebo . PTX was well tolerated in patients with NASH 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 , prospect i ve , placebo-controlled study , 64 patients with ACS were r and omized 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)-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 Oxpentifylline ( pentoxifylline ) , which is known to have pharmacological effects in animal models of respiratory distress syndrome , multiorgan failure , and shock , was tested in human beings after injection of endotoxin . Of ten healthy volunteers , nine met the inclusion criterion of a rise in body temperature of at least 1.0 degrees C after 100 ng endotoxin ( Salmonella abortus equi ) as a bolus injection .  Serum levels of tumour necrosis factor alpha ( TNF ) and interleukin-6 ( IL-6 ) were both significantly higher than baseline levels 2 h and 3 h after endotoxin injection . 3 weeks later the nine volunteers were again injected with 100 ng endotoxin and oxpentifylline ( 500 mg over 4 h ) was also infused . There was no rise in TNF levels , though IL-6 levels rose in parallel with body temperature . These data suggest that oxpentifylline blocks the endotoxin-induced synthesis of TNF in man and , therefore , could possibly have beneficial effects in clinical endotoxaemia OBJECTIVES Inflammation and oxidative stress are main culprits behind atherosclerosis in diabetes mellitus . This study explores the effect of add-on Pentoxifylline on inflammatory burden and oxidative stress in hypertensive diabetic patients . RESEARCH DESIGN AND METHODS 60 hypertensive type 2 diabetic , aged > or = 45 years were evaluated for anthropometry , clinical parameters , C-reactive protein , total leukocyte count , erythrocyte sedimentation rate , serum albumin , plasma malondialdehyde , blood reduced glutathione , platelet aggregation and clot retraction profile . With informed consent and r and omization , Pentoxifylline ( 400 mg ) was prescribed to 30 patients orally twice daily with meals as add-on therapy to the st and ard therapeutic regimen for one month . The particular parameters were repeated in 26 patients in control group and 25 patients in Pentoxifylline group who completed the follow up . The study was a r and omized , open , add-on clinical trial with parallel controls . RESULTS At one-month follow-up , in the Pentoxifylline group , there was 20.9 % decrease ( p<0.001 ) in C-reactive protein , 18 % reduction ( p<0.001 ) in erythrocyte sedimentation rate , 11.1 % reduction ( p<0.001 ) in total leukocyte count and 5.8 % increase ( p=0.003 ) in serum albumin .  Pentoxifylline showed 20.2 % reduction in plasma malondialdehyde and 4.6 % increase in blood reduced glutathione level . In therapeutic dose range , Pentoxifylline exerted a significant anti-aggregatory effect and a dose dependent decrease in clot retraction in-vitro but there was no significant change in ex-vivo clot retraction . The control group showed no statistically significant change in parameters assessed . CONCLUSION This study reveals improvements in inflammatory markers , oxidative stress and platelet-aggregation by Pentoxifylline , thus preventing atherosclerosis in diabetes mellitus Pentoxifylline ( PTX ) is a nonselective phosphodiesterase inhibitor that inhibits the production of TNFalpha and IL6 and IL-10 cytokines . In renal rejection TNFalpha , IL-6 , and IL-10 may have important roles . In this study , 22 renal transplant recipients treated with tacrolimus , prednisolone , and mycophenolate mofetil  were prescribed PTX ( 2 x 600 mg/d ) for 3 months ( GI ) , and 20 similar patients not receiving PTX  were used as controls ( GII ) . Stable subjects whose serum creatinine was lower than 1.8 mg/dL and were more than 6 months posttransplant , were enrolled into this study if the blood pressure was well controlled and there was no  diabetes mellitus , infection , or  inflammation . At the end of 3 months TNF-alpha decreased from 4.2 + /- 2.1 to 2.4 + /- 0.7 ( P = .001 ) and 4.0 + /- 2.2 to 3.9 + /- 1.7 ( P = .718 ) , IL-10 also decreased from 3.90 + /- 1.9 to 2.38 + /- 0.6 ( P = .001 ) and 4.02 + /- 1.6 to 3.82 + /- 1.5 ( P = .225 ) in GI and GII , respectively . For IL-10 and TNF-alpha the alterations between baseline and the last visit of GI and GII were significant ( P < .002 for all ) . Resistive index ( RI ) decreased in GI but the difference in alterations between baseline and the last visit of GI and GII was marginal . In summary IL-10 and TNF-alpha levels decreased in stable recipients treated with PTx . RI also decreased marginally secondary to PTx treatment . PTx was well tolerated and free side effects .  PTx did not affect tacrolimus levels or other biochemical and hematological parameters Diabetic kidney disease ( DKD ) is the leading cause of ESRD . We conducted an open-label , prospect i ve , r and omized trial to determine whether pentoxifylline ( PTF ) , which reduces albuminuria , in addition to renin-angiotensin system ( RAS ) blockade , can slow progression of renal disease in patients with type 2 diabetes and stages 3 - 4 CKD . Participants were assigned to receive PTF ( 1200 mg/d ) ( n=82 ) or to a control group ( n=87 ) for 2 years . All patients received similar doses of RAS inhibitors . At study end , eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m(2 ) in the PTF group compared with 6.5±0.4 ml/min per 1.73 m(2 ) in the control group , with a between-group difference of 4.3 ml/min per 1.73 m(2 ) ( 95 % confidence interval [ 95 % CI ] , 3.1 to 5.5 ml/min per 1.73 m(2 ) ; P<0.001 ) in favor of PTF . The proportion of patients with a rate of eGFR decline greater than the median rate of decline ( 0.16 ml/min per 1.73 m(2 ) per month ) was lower in the PTF group than in the control group ( 33.3 % versus 68.2 % ; P<0.001 ) . Percentage change in urinary albumin excretion was 5.7 % ( 95 % CI , -0.3 % to 11.1 % ) in the control group and -14.9 % ( 95 % CI , -20.4 % to -9.4 % ) in the PTF group ( P=0.001 ) . Urine TNF-α decreased from a median 16 ng/g ( interquartile range , 11 - 20.1 ng/g ) to 14.3 ng/g ( interquartile range , 9.2 - 18.4 ng/g ) in the PTF group ( P<0.01 ) , with no changes in the control group . In this population , addition of PTF to RAS inhibitors result ed in a smaller decrease in eGFR and a greater reduction of residual albuminuria BACKGROUND Pentoxifylline ( PTF ) is a potential therapeutic agent in chronic kidney disease due to its antiinflammatory and antiproteinuric effects that may influence the progression of renal disease . SUBJECTS AND METHODS We conducted a prospect i ve r and omized trial of 91 patients with estimated glomerular filtration rate ( eGFR ) < 60 ml/min , calculated with 4-variable Modification of Diet in Renal Disease ( MDRD-4 ) Study equation . Patients were r and omly assigned to treatment with PTF 400 mg ( twice a day ) ( n=46 ) or to continue their usual therapy ( n=45 ) . Clinical , biochemical and inflammatory parameters were measured at baseline , and at 6 and 12 months of treatment . The objective of the study was to analyze the effect of PTF treatment on inflammatory markers and secondarily the effect on renal disease progression . RESULTS Baseline characteristics were similar in the 2 groups .  High-sensitivity C-reactive protein ( hs-CRP ) , serum fibrinogen and TNF-alpha decreased significantly in patients treated with PTF in comparison with the control group at 12 months ( p=0.002 , p=0.001 and p=0.000 , respectively ) . Median urinary albumin excretion did not decrease with PTF treatment . In the PTF group , there was no significant change in eGFR after 12 months ( from 42.3 ± 10.2 to 44.7 ± 11.3 ml/min per 1.73 m(2 ) ) , whereas in the control group there was a worsening by the end of the study ( from 40.1 ± 12.4 to 35.7 ± 13.4 ml/min per 1.73 m(2 ) ) ( p=0.000 between groups ) . CONCLUSIONS PTF treatment decreases inflammatory markers in chronic kidney disease and stabilizes renal function
target: No alteration in plasma IL-6 concentration was observed .
  Pentoxifylline did not alter BP or plasma IL-6 concentration , but significantly reduced circulating TNF-α and CRP concentrations
background: INTRODUCTION Pentoxifylline is a xanthine derivative with potential cardiovascular benefits .
  AIM To evaluate the impact of pentoxifylline on  blood pressure ( BP )  and plasma TNF-α , C-reactive protein ( CRP ) and IL-6 through a systematic review and meta- analysis of r and omized controlled trials .