Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease--a randomized placebo-controlled study. Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline: Results of a Randomized Study Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms. Leukocyte Activation Study During Occlusive Arterial Disease of the Lower Limb: Effect of Pentoxifylline Infusion Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension Intermittent claudication: a double-blind crossover trial of pentoxifylline. A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH) Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus Effect of Pentoxifylline on inflammatory burden, oxidative stress and platelet aggregability in hypertensive type 2 diabetes mellitus patients. The effects of pentoxifylline on liver regeneration after portal vein ligation in rats. Mediator effects of parameters of inflammation and neurogenesis from a N-acetyl cysteine clinical-trial for bipolar depression. The impact of time on the systemic inflammatory response in pneumococcal pneumonia Production of Proinflammatory Cytokines and Cytokines Involved in the TH1/TH2 Balance Is Modulated by Pentoxifylline Pentoxifylline in the Treatment of Intermittent Claudication of the Lower Limbs Effect of 10-day broccoli consumption on inflammatory status of young healthy smokers Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy Resting blood pressure reductions following isometric handgrip exercise training and the impact of age and sex: protocol for a systematic review
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 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 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 Granulocytes play a significant role in vascular diseases . The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators . Pentoxifylline ( PTX ) has a well-demonstrated ability to act on the activated neutrophils . It increases chemotaxis and decreases their adherence to endothelial cells , oxidative burst , and enzyme release . In this preliminary study , we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils ( PMN ) activation and cytokine release . A double-blind , r and omized , placebo-controlled trial was carried out in 14 patients ( age range 46–86 years ) suffering from critical ischemia , as defined by the European Consensus Document , or sub-acute ischemia due to occlusive arterial disease of the lower limb . Femoral and antecubital venous blood sample s on the side of the ischemic leg were obtained from patients immediately before ( TO ) and after infusion ( T24 ) of PTX or placebo . PMN activation was evaluated by study of cell migration , β2 integrin expression ( CD11b/GD18 ) , oxidative burst , and elastase release . Inflammation proteins were analyzed , such as tumor necrosis factor-α ( TNF-α ) , interleukin-1 ( IL-1 ) , interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) , and fibrinogen . Before treatment , our results demonstrate an important activation in both femoral and antecubital venous blood . PMN activation markers , cytokine release , and other inflammation proteins were significantly increased compared with normal subjects . In the experimental group there was no significant difference between femoral and antecubital venous blood . Six patients received PTX infusion and seven patients were in the placebo group . The effect of PTX was evaluated after 24 h of treatment ( 1,200 mg ) . In the PTX group the following variables were improved compared with the placebo group : CD11b expression on PMNs , elastase released from PMNs , fibrinogen , CRP , TNF-α , and IL6 in plasma . These preliminary results should be interpreted with caution because of the small sample size . Further trials may contribute to more complete underst and ing High blood pressure ( HBP ) has been associated with elevated C-reactive protein ( CRP ) , a marker of chronic mild inflammation . However , the association between HBP and other inflammatory markers , particularly interleukin 6 ( IL-6 ) and tumour necrosis alpha ( TNF-α ) , has not been evaluated in well-controlled studies . We examined the cross-sectional relationship between IL-6 , TNF-α , and CRP and HBP in a r and om sample of 196 healthy subjects . All markers were measured in duplicate with high-sensitivity ELISA tests . Three blood pressure ( BP ) measurments were averaged for the analysis , and subjects with systolic BP ⩾140 and /or diastolic BP ⩾90 mmHg were considered hypertensive . Log binomial regression was used to estimate multivariate-adjusted prevalence ratios ( PR ) of HBP . Of the subjects , 40 % ( 79 ) were hypertensive ( mean age : 44 years ; range 30–64 ) . After adjustment for age , sex , body mass index , family history of HBP , and the level of the other inflammatory markers , subjects in the second ( PR : 3.10 , P=0.003 ) , third ( PR : 2.32 ; P=0.031 ) , and fourth quartiles ( PR : 2.30 ; P=0.036 ) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile . Corresponding PR estimates for TNF-α levels were 1.41 ( P=0.014 ) for the second ; 1.59 ( P=0.001 ) for the third ; and 1.61 ( P=0.025 ) for the fourth quartile . The CRP – HBP association was not statistically significant . Our results suggest that TNF-α and IL-6 could be independent risk factors for HBP in apparently healthy subjects . Nevertheless , the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospect i ve cohort studies The influence of the xanthine derivative pentoxifylline ( ' Trental ' or BL191 ; Hoechst-Roussel ) on exercise tolerance was measured in 38 subjects with stable , severe to moderately severe , intermittent claudication who completed a r and omised , double-blind , placebo controlled , cross-over clinical trial . Patients received placebo tablets or 400 mg slow-release pentoxifylline tablets ( ' Trental 400 ' ) twice a day for one week , followed by three times daily for seven weeks , and then crossed over to receive the alternate preparation for another eight weeks . Claudication distance and walking distance were measured on a treadmill before starting treatment and again at four-week intervals during the trial . At the same times , red blood cell filterability , plasma fibrinogen concentration and blood viscosity , resting and post-ischemic calf muscle blood flow , and the resting and post-exercise ankle/brachial systolic pressure ratio were also measured . In this study , the observed effects of  pentoxifylline treatment were no greater than those of placebo , even though serum levels of pentoxifylline and its hydroxy-metabolite were within the anticipated range . This was shown by a ' therapeutic effect ratio ' of 0.98 for treadmill claudication distance and 0.96 for treadmill walking distance after within-patient analysis at the end of the cross-over ( where a ratio of 1.0 means the test drug and placebo effects are identical ) . These ratios have 95 % confidence limits of 0.72 - 1.34 and 0.74 - 1.25 , respectively Purpose Tumor necrosis factor-α ( TNF-α ) is implicated in non-alcoholic steatohepatitis ( NASH ) . Pentoxifylline inhibits TNF-α . We wanted to evaluate the efficacy of Pentoxifylline on NASH patients . Methods Patients with biopsy proven NASH and persistently elevated alanine aminotransferase ( ALT ) greater than 1.5 times the upper limit of normal were r and omized to 3 months of treatment with a step 1 American Heart Association diet and daily exercise with Pentoxifylline or placebo . Liver function tests , serum lipids and TNF-α , Interleukin 6 ( IL-6 ) , and plasma hyaluronic acid were measured at baseline , at weeks 6 and 12 . Categorical data were analyzed by Fisher ’s exact test while independent sample t-test and Mann – Whitney test were used for continuous data . Results Eleven patients were r and omized into the Pentoxifylline and nine to the placebo group . After 3 months of treatment body mass index ( BMI ) , ALT and aspartate aminotransferase ( AST ) decreased significantly in both groups . There was no difference between the two groups in reduction of BMI ( P = 0.897 ) . There was significantly greater reduction in AST in the Pentoxifylline group ( P = 0.038 ) . There was a trend toward lower ALT level ( P = 0.065 ) in the Pentoxifylline  group . TNF-α and IL-6 decreased significantly in both groups after treatment , but there was no significant difference between the two groups . Conclusion Three months of Pentoxifylline treatment in combination with diet and exercise results in significantly greater reduction in AST levels in patients with NASH as compared with controls Summary The effects of an infusion of pentoxifylline 1 g as an inhibitor of free radical generation have been determined in a double-blind placebo-controlled study . Leucocyte-derived free radical generation ( by the superoxide dismutase-inhibitable reduction of ferricytochrome ) , the release of reactive oxygen metabolites ( as plasma oxidant activity ) , unfractionated leucocyte and erythrocyte filterability rates ( using a constant-flow positive-pressure system ) , plasma viscosity , and plasma fibrinogen concentration have been measured in two matched groups of 10 patients with Stage II peripheral vascular disease , before and after treatment .  Transcutaneous oxygen pressure ( PtcO2 ) during treadmill exercise to stress leg circulation was also measured . Leucocyte-derived free radicals were generated during peripheral ischaemia . Pentoxifylline inhibited their generation , blocked the release of reactive oxygen metabolites , and reduced impairment of the filterability rate of unfractionated leucocytes . The improvements were accompanied by significant shortening of the half-time of recovery of transcutaneous oxygen pressure , indicating that ischaemic damage had been contained Background Diabetes mellitus ( DM ) and chronic inflammation are strongly related to increased cardiovascular risk . The purpose of this study was to evaluate whether an aerobic training programme would ameliorate inflammatory and anti-inflammatory markers in patients with type 2 DM . Design Interventional study . Methods A total of 60 overweight individuals with type 2 DM , but without vascular complications , were r and omly assigned to either a 6-month aerobic exercise training programme ( four times/week , 45 - 60 min/session ) , design ated as exercise group , or to the control group .  All participants were on an oral antidiabetic regimen and none was receiving lipid-lowering medications . Anthropometric parameters , cardiorespiratory fitness , glycaemic and lipid profiles , high sensitivity C-reactive protein ( hs CRP ) , adiponectin , interleukin (IL)-10 , IL-18 , tumour necrosis factor (TNF)-a , insulin , reciprocal index of homoeostasis model assessment ( HOMA-IR ) , body fat and blood pressure ( BP ) were measured at baseline and at the end of the study . Results In comparison with baseline and control group , exercise-treated patients improved glucose control , lipid profile , exercise capacity ( Vo2 peak ) and exhibited decreased insulin resistance and systolic BP considerably ( P < 0.05 ) . Plasma adiponectin , TNF-α and body weight changed slightly across treatment ( P > 0.05 ) , whereas diastolic BP and fat mass tended to decrease ( P = 0.071 and 0.061 , respectively ) . Exercise training  reduced hs CRP ( from 0.48 ± 0.16 to 0.29 ± 0.2 mg/dl ; P = 0.04 ) and IL-18 ( from 315.19 ± 122.76 to 203.77 ± 96.02 pg/ml ; P = 0.02 ) . Moreover , exercise  provided anti-inflammatory protection through IL-10 increment ( P = 0.039 ) and IL-18/IL-10 ratio downregulation ( P = 0.014 ) . In multiple regression analysis , alteration in IL-18 was independently correlated with hs CRP and Vo2 peak changes ( P < 0.05 ) . Conclusion Aerobic exercise training without significant weight loss improves metabolic profile and exerts anti-inflammatory effects in patients with type 2 DM . Eur J Cardiovasc Prev Rehabil 14 : 837 - 843 © 2007 The European Society of 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 AIM To determine the effects of pentoxifylline , a methyl xanthine derivative on hepatic cell production of uninterferred lobe after portal vein branch ligation . METHODS Sixty-six rats were r and omly allocated into 9 groups with 8 rats in PVL groups and 6 rats in sham operation groups . The portal branches of the median and the lateral liver lobes , corresponding to approximately 70 % of the liver volume were ligated in the PVL groups . The control group received 0.9 % NaCl solution . The rats in the treatment groups received pentoxifylline at the dose of 50 mg/kg/dy . After 1 , 2 , 4 days of portal vein ligation in both PVL and PVNL lobes the levels of adenine nucleotides were determined and flowcytometric analysis of cell cycles were performed . RESULTS On the first day of portal branch ligation energy charge was significantly lower , in pentoxifylline treated group comparing to pentoxifylline untreated group , both in PVL and PVNL lobes ( P<0.05 ) . Proliferative indexes were 0.38 and 0.29 in pentoxifylline treated and pentoxifylline untreated PVNL lobes respectively ( P<0.05 ) . CONCLUSION Pentoxifylline treatment result ed in an increase of percentage of calls entering mitosis phase on the first day after PVL , somehow accelerating the regeneration process OBJECTIVE This study aim ed to explore effects of adjunctive treatment with N-acetyl cysteine ( NAC ) on markers of inflammation and neurogenesis in bipolar depression . METHODS This is a secondary analysis of a placebo-controlled r and omised trial . Serum sample s were collected at baseline , week 8 , and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6 , IL-8 , IL-10 , tumour necrosis factor-α ( TNF-α ) , C-reactive protein ( CRP ) and brain-derived neurotrophic factor ( BDNF ) following adjunctive NAC treatment , and to explore mediation and moderator effects of the listed markers . RESULTS Levels of brain-derived neurotrophic factor ( BDNF ) , tumour necrosis factor-α ( TNF-α ) , C-reactive protein ( CRP ) , interleukins ( IL ) -6 , 8 , or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases . There were no mediation or moderation effects of the biological factors on the clinical parameters . CONCLUSION The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression The aim of our study was to analyse the impact of time from onset of symptoms on the systemic cytokine concentrations in patients with pneumococcal pneumonia . Adults with severe pneumococcal pneumonia were prospect ively included . At admission , vital signs , time from onset of pneumonia symptoms and circulating levels of C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , tumour necrosis factor (TNF)-α , and interleukin (IL)-1β , IL-6 , IL-8 , IL-10 and IL-1ra were recorded . 32 patients were included ; 13 patients had < 48 h of evolution and 19 patients had been sick for > 48 h. The group with a longer time of evolution presented higher plasmatic levels of TNF-α ( 19.1±8.5 versus 35.5±26 pg·mL−1 ) , fibrinogen ( 6±1.8 versus 9±2 ) ; CRP ( 130±85 versus 327±131 ) and SAA ( 678±509 versus 984±391 ) . Concentrations of TNF-α were associated with the presence of bacteraemia , initial blood pressure < 90 mmHg and with a lower oxygen saturation at admission . Likewise , TNF-α levels were correlated with concentrations of IL-1β ( r = 0.49 ) , IL-6 ( r = 0.41 ) and IL-8 ( r = 0.40 ) . In pneumococcal pneumonia , patients with a longer time of evolution presented with higher levels of pro-inflammatory cytokines and a higher expression of acute phase proteins , suggesting a sustained release of pneumococcal antigens over time The modulation of cytokine release induced by pentoxifylline ( PTX ) has recently been demonstrated not to be restricted solely to tumor necrosis factor (TNF)-α . This prompted us to study the influence of PTX on a larger spectrum of cytokines with proinflammatory actions [ TNF-α , interleukin-6 , (IL)-6 , IL-1β , IL-8 ] or with implied actions in the TH1 ( IL-2 , IFN-γ)/TH2 ( IL-10 ) balance . The IL-1RA was also explored . This work was performed using a whole-blood model in which cytokine production is measured after stimulation by lipopolysaccharide ( LPS ) ( 25 μg/ml ) and phytohemagglutinin ( PHA ) ( 5μg/ml ) in 1:10 diluted whole blood . The stimulation test was performed in blood from healthy controls and from septic patients ( without septic shock ) in the presence or absence of PTX at 10–6 , 10–5 , 10–4 , or 10–3 M. In controls and septic patients , at a 10–4 M PTX  concentration the production of IL-2 is strongly diminished ( 26–32 % of the basal level ) , followed by diminution of IFN-γ ( 30–40 % ) . As expected , of the proinflammatory cytokines TNF was the most strongly suppressed ( 50 % of baseline ) followed by IL-1 ( about 80 % of basal production ) . Finally , IL-10 was also influenced by PTX ( 65 % of baseline ) . At 10–4 M , IL-1RA and IL-6 were unaffected by PTX . Taken altogether , our data demonstrate that PTX possesses a much broader spectrum of activity on cytokine production than was initially described , and it appears to be a potential and promising immunotherapeutic agent Pentoxifylline , a methyl xanthine analogue was evaluated for treatment of intermittent claudication in a double-blind placebo controlled parallel group study in seven centers in the United States . Tests were performed on 128 cases , including 42 who took pentoxifylline ( 600 mg by mouth daily , increased stepwise to 1200 mg daily at the end of one month ) and 40 who took placebo for 24 weeks . Twenty-five patients on pentoxifylline and 21 on placebo were dropped from the study for reasons unrelated to the drug . Walking ability on a treadmill was increased significantly after 2 weeks and remained so throughout the study in the pentoxifylline vs. the placebo group . Ability to walk until first experiencing intermittent claudication was a more sensitive index than the maximum ability to walk . The drug did not cause changes in blood pressure or in heart rate . Other than mild nausea , there were no significant side effects Abstract This study evaluated the effects of 10-day broccoli ( 250 g/day ) intake on dietary markers and markers of inflammations in young male smokers . A dietary intervention study with a repeated measures crossover design was conducted . Circulating levels of carotenoids , folate , C-reactive protein ( CRP ) , tumor necrosis factor alpha ( TNF-α ) , interleukin 6 ( IL-6 ) , interleukin 6 receptor ( IL-6sR ) and adiponectin were measured . Broccoli intake significantly increased plasma levels of folate ( + 17 % ) and lutein ( + 39 % ) , while no significant effect was observed for TNF-α , IL-6 , IL-6sR or adiponectin . Plasma CRP decreased by 48 % ( post-hoc analysis , p < 0.05 ) following broccoli diet ; this result ed to be independent from the plasma variations in lutein and folate . An inverse correlation between lycopene , TNF-α and IL-6sR was observed at baseline . In conclusion , broccoli consumption may reduce CRP levels in smokers , consistent with epidemiologic observations that fruit and vegetable intake is associated with lower circulating CRP concentrations 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 Background The risk of developing cardiovascular disease is directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex . Resting BP can be reduced using h and grip exercise training , but the impact of age and sex on the effectiveness of training is not well documented . Methods / design A systematic search of the literature will be conducted for all experimental studies ( including r and omized controlled trials and prospect i ve experiments ) that report the influence of isometric h and grip exercise training on resting systolic blood pressure . The data bases Medline , Embase , Cochrane Review s , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , SPORTD iscus , Web of Science , Allied and Complementary Medicine ( AMED ) , PubMed , and Scopus will be search ed until 1 December 2015 . Screening of potential articles , data abstract ion , and quality appraisal will be completed in duplicate independently . When necessary , corresponding authors will be contacted in order to facilitate the separation of pooled data into age and sex categories . Method ological quality will be determined using the Quality Assessment Framework developed by the Cochrane Collaboration and the Newcastle-Ottawa Quality Assessment Scale as appropriate . Any discrepancies will be resolved by a third author . Findings will be presented in accordance with the preferred reporting items for systematic review s and meta- analysis ( PRISMA ) guidelines . Discussion This systematic review will determine the overall effectiveness  of h and grip exercise training in improving resting blood pressure . A novel , focused assessment will contrast  effectiveness of h and grip training  based on the age ( younger 18–54 years , older > 55 years ) and the sex ( men , women ) of study participants . This information is essential to consoli date before moving forward with the development and implementation of h and grip exercise training programmes which are design ed to best meet the needs of particular cohorts . Systematic review registration PROSPERO
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
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 .