Disease relevance of pentoxifylline

• Pentoxifylline in the treatment of children with new-onset type I diabetes mellitus [1].
• Pentoxifylline inhibits interleukin-2-induced toxicity in C57BL/6 mice but preserves antitumor efficacy [2].
• Also, treatment of HCMV-stimulated PBMC with pentoxifylline, an inhibitor of TNF-alpha mRNA, markedly reduced HIV-1 replication in cocultures both with acutely and chronically infected cells [3].
• Pentoxifylline for treatment of venous leg ulcers: a systematic review [4].
• Pentoxifylline significantly decreased proteinuria from 11 g/day [range 4.6-27] to 1.8 (0-10.9); p=0.001) [5].
• In this study pentoxifylline did not protect against post-ERCP pancreatitis or hyperamylasemia [6].

Psychiatry related information on pentoxifylline

• OBJECTIVE: To review the evidence for efficacy of three contemporary treatments for intermittent claudication: pentoxifylline, exercise programs, and smoking cessation [7].
• Yohimbine and pentoxifylline in the treatment of erectile dysfunction [8].
• Pentoxifylline and panic attacks [9].
• Pentoxifylline-induced musical hallucinations [10].
• Non-hormonal therapy includes improvement of testicular microcirculation by oxpentifylline, antimicrobial and anti-inflammatory agents, drugs to improve or allow emission and ejaculation, and psychotropic and antispasmodic drugs to diminish functional disturbances induced by emotional stress [11].

High impact information on pentoxifylline

• Down-regulation of Kupffer cells with calcium blockers or pentoxifylline improves graft survival, whereas priming with lipopolysaccharide or alcohol worsens survival [12].
• c-Rel is a target of pentoxifylline-mediated inhibition of T lymphocyte activation [13].
• TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively [14].
• IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h [14].
• In RAW 264.7 macrophages, pentoxifylline blocks cachectin/TNF mRNA accumulation but has no effect upon the efficiency of reporter mRNA translation [15].

Chemical compound and disease context of pentoxifylline

• Because pentoxifylline (PTXF) inhibits TNF production, we hypothesized that PTXF would ameliorate IL-2 toxicity without compromising antitumor efficacy [2].
• Synergistic effects of pentoxifylline and dapsone in leucocytoclastic vasculitis [16].
• Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial [17].
• Subgroup analysis disclosed that, in patients with isolated mitral valve replacement, warfarin was superior to both of the PSTs with respect to the prevention of thromboembolism (warfarin vs dipyridamole-aspirin, p = .005; warfarin vs pentoxifylline-aspirin, p less than .05) [17].
• This activation was unaffected by PTX when NF-kappa B sites in the HIV-1 LTR were mutated, suggesting that this drug does not directly influence Tat function, which, however, was inhibited by the Tat-inhibitor Ro 24-7429 [18].

Biological context of pentoxifylline

• Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees [19].
• To potentially intervene in the molecular pathways elicited by endotoxin, pentoxifylline, an agent that interrupts "immediate early" gene activation by monocytes, or a potent monoclonal antibody that neutralizes tissue factor-mediated initiation of coagulation, were infused shortly before endotoxin [19].
• The anti-oxidants N-acetyl cysteine (NAC) or pentoxifylline (PTX), which are used clinically to reduce NF-kappa B/Rel activity, inhibited NF-kappa B driven promoter transactivation, and SMC-Rel binding activity [20].
• Pentoxifylline prevented up-regulation of TNF-alpha expression [21].
• This study aimed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy [22].

Anatomical context of pentoxifylline

• Combined application of dexamethasone and pentoxifylline to macrophages causes a greater suppression of cachectin/TNF biosynthesis that can be achieved by either agent alone [15].
• METHODS: Rats were treated with several doses of indomethacin alone or in association with substances known to increase (interleukin 2 and lipopolysaccharide) or inhibit (pentoxifylline, dexamethasone, granulocyte colony-stimulating factor [G-CSF]) TNF synthesis and release [23].
• Each treated group disclosed better portal flow and sinusoid perfusion, decreased leukocyte adherence, particularly in the PTX group [24].
• Noncytotoxic concentrations of the drug pentoxifylline (PTX) inhibited interaction of NF-kappa B with its motif and the stimulation of HIV-1 LTR-driven gene expression in Jurkat cells [18].
• Localization of transfused neutrophils to site of infection during treatment with recombinant human granulocyte-macrophage colony-stimulating factor and pentoxifylline [25].

Associations of pentoxifylline with other chemical compounds

• Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway [15].
• Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively [14].
• Linomide, but not thalidomide or pentoxifylline, increased production of PAI-2 by human macrophages [26].
• Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] is a unique metabolite of pentoxifylline in humans and is > 800-fold more active as an inhibitor of PA formation than pentoxifylline (IC50 = 0.6 microM) [27].
• Intensive vascular training in stage IIb of peripheral arterial occlusive disease. The additive effects of intravenous prostaglandin E1 or intravenous pentoxifylline during training [28].

Gene context of pentoxifylline

• IL-6 and IL-10 levels were dramatically up-regulated (50x) in the PTX group, and at lower levels in other experimental groups [24].
• We have also demonstrated that the adhesion of tumor cells to IL-1 beta-treated human umbilical vein endothelial cells can be inhibited by anti-NF kappa B reagents such as N-acetyl L-cysteine, aspirin, or pentoxifylline [29].
• In intoxicated obese mice, pentoxifylline fully prevented the increase in plasma TNF-alpha the decrease in nuclear NF-kappaB activity, and the increase in hepatic caspase-3, and it also decreased hepatic triglycerides [30].
• Interestingly, the grafts from the PTX-treated recipients continued to display rare, isolated VCAM-1 positive cells in the interstitium, which may be dendritic cells [31].
• We report that the expression of VCAM-1 on isograft endothelia that was induced with anti-CD3 MAb was blocked by simultaneous treatment with either pentoxifylline, soluble tumor necrosis factor (TNF) receptor (TNFR-Fc), anti-IL4 MAb, or soluble IL4R, but not by anti-IFN-gamma MAb [32].

Analytical, diagnostic and therapeutic context of pentoxifylline

• 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 [33].
• Partial 30% liver transplantation was performed in C57BL/6 wild-type mice (control group), and in three groups with down-regulation of the TNF-alpha pathway: (i) TNF receptor 1 knockout [TNFR-1(-/-)] mice, and mice pretreated with (ii) gadolinium chloride or (iii) pentoxifylline (PTX) [24].
• A randomized controlled trial of pentoxifylline for the prevention of regimen-related toxicities in patients undergoing allogeneic marrow transplantation [34].
• Papaverine and pentoxifylline administered during preservation and at the time of reperfusion significantly improved all parameters [35].
• Effects of pentoxifylline pretreatment on Kupffer cells in rat liver transplantation [36].

References