Pentoxifylline inhibits lipopolysaccharide-induced serum tumor necrosis factor and mortality

Noel, Phillip; Nelson, Steve; Bokulic, Ronald E.; Bagby, Gregory J.; Lippton, Howard; Lipscomb, Gary; Summer, Warren R.

doi:10.1016/0024-3205(90)90474-6

Cited by 85 publications

(48 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The PDE4 inhibitors have been proposed as antiin¯ammatory drugs (Sekut et al, 1995;Ortiz et al, 1996;Teixeira et al, 1997;Cheng et al, 1997;Goncalves de Moraes et al, 1998). Our results of pentoxifylline accord with previous studies to demonstrate that this non-selective PDE inhibitor has an anti-in¯ammatory property by inhibiting TNF-a release (Noel et al, 1990;Neuner et al, 1994;Schratzberger et al, 1999). PDE3 inhibitors are clinically used for congestive heart failure.…”

Section: Discussionsupporting

confidence: 88%

“…PDE inhibitors have been shown to suppress LPSstimulated TNF-a release in both in vivo and in vitro studies (Pettipher et al, 1996;Noel et al, 1990;Sekut et al, 1995;Teixeira et al, 1997;Gantner et al, 1997;Goncalves de Moraes et al, 1998), and to have anti-in¯ammatory e ects in airway in¯ammation models and carrageenaninduced paw oedema (Sekut et al, 1995;Ortiz et al, 1996;Teixeira et al, 1997). Our study demonstrated the antiin¯ammatory e ects of PDE inhibitors using a LPS-induced microvascular leakage in mice skin.…”

Section: Discussionsupporting

confidence: 57%

See 1 more Smart Citation

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Irie

Fujii

Ishida

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

1 Anti-in¯ammatory e ects of cyclic AMP elevating agents were examined in a mouse model of lipopolysaccharide (LPS)-induced microvascular permeability change. 2 Vascular permeability on the back skin was measured by the local accumulation of Pontamine sky blue (PSB) after subcutaneous injection of LPS (400 mg site 71 ) from Salmonella typhimurium. 3 Dye leakage in the skin was signi®cantly increased 2 h after injection of LPS. This LPS-induced dye leakage was suppressed by phosphodiesterase inhibitors, including pentoxifylline (160 mg kg 71 ), milrinone (5 ± 10 mg kg 71 ), rolipram (0.5 ± 10 mg kg 71 ) and zaprinast (5 ± 10 mg kg 71 ). The dye leakage was also inhibited by b-adrenoceptor agonists, including isoproterenol (0.5 ± 5 mg kg 71 ) and salbutamol (0.05 ± 5 mg kg 71 ), an adenylate cyclase activator, forskolin (5 mg kg 71 ), and a cell permeable cyclic AMP analogue, 8-bromo-cyclic AMP (8-Br-cAMP, 10 mg kg 71 ). 4 LPS caused a transient increase in serum TNF-a level peaking at 1 h after the injection. This increase in serum TNF-a was completely blocked by a pretreatment with pentoxifylline (160 mg kg 71 ), milrinone (5 mg kg 71 ), rolipram (1 mg kg 71 ), zaprinast (10 mg kg 71 ), salbutamol (0.5 mg kg 71 ), forskolin (1 mg kg 71 ) and 8-Br-cAMP (10 mg kg 71 ). 5 LPS caused an increase in serum IL-1a level peaking at 3 h after injection. This increase in serum IL-1a was not signi®cantly suppressed by the cyclic AMP elevating agents. 6 Our study suggests that cyclic AMP elevating agents attenuate LPS-induced microvascular permeability change by suppressing TNF-a up regulation.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 57%

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Irie

Fujii

Ishida

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…In vivo, pentoxifylline has been shown to decrease the action of inflammatory agents on host tissues in several different systems. Pentoxifylline decreases inflammatory tissue damage in animal models of endotoxic shock (33,44,52,65), hemorrhagic shock (3, 64), IL-2 induced lung injury (30), and bacterial meningitis (50). Pentoxifylline decreased nephrotoxicity associated with AmB and cyclosporin treatment in patients receiving allograft bone marrow transplants (8).…”

Section: Resultsmentioning

confidence: 99%

Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro

Sullivan

Carper

Mandell

1992

Antimicrob Agents Chemother

View full text Add to dashboard Cite

a second stimulus. AmB also stimulates mononuclear leukocytes (MNLs) to release inflammatory mediators which augment the effects of AmB on PMN function. In the present study, we observed that the methylxanthine derivative pentoxifylline decreased the effects of AmB on PMN function. AmB (2 ,ug/ml) priming doubled PMN chemiluminescence stimulated by fMet-Leu-Phe. In the presence of MNLs, AmB priming increasedjMet-Leu-Phe-stimulated PMN chemiluminescence to 622% of unprimed PMN activity. Pentoxifylline (100 ,uM) blunted the rise in AmB-augmented PMN chemiluminescence in the presence of MNLs to 282% of unprimed PMN activity, and pentoxifylline metabolites were active at 10 ,IM. Pentoxifylline (100 ,uM) also blocked AmB-augmented PMN oxidative activity in whole blood, as measured by nitroblue tetrazolium reduction. In the presence of MNL, AmB (2 ,ug/ml) doubled the expression of the important PMN adherence factor Mac-1. Pentoxifylline (1 mM) decreased AmB-stimulated PMN Mac-i expression back to unstimulated amounts. In the presence of MNLs, AmB (2 jig/ml) decreased PMN nondirected and directed migration to fMet-Leu-Phe to 40 and 38% of control PMN migration, respectively. Pentoxifylline (300 ,uM) counteracted AmB inhibition of nondirected and directed migration to fMet-Leu-Phe, resulting in migration that was 71 and 87% of control PMN migration, respectively. In contrast, the methylxanthine caffeine (100 ,iM) increased AmB-enhanced chemiluminescence but did not affect AmBinhibited PMN migration. Pentoxifylline should be evaluated as adjunctive therapy to lessen the inflammatory damage caused by AmB.The antifungal agent amphotericin B (AmB) has a stimulatory effect on several polymorphonuclear leukocyte (PMN) functions. AmB increases PMN adherence to nylon wool, PMN aggregation (5,9,10,35,40,69), and PMN oxidative activity (59). AmB also activates macrophages (15,34,48,66,67) and induces the production of tumor necrosis factor alpha (TNF-ot) and interleukin-1 beta 8) (17,25). We have observed that the presence of mononuclear leukocytes (MNLs) exacerbates the inflammatory effects of AmB on PMN function, including AmB priming of the PMN oxidative burst and PMN expression of the adherence inte-

show abstract

“…PTX is a phosphodiesterase inhibitor that has been shown to decrease TNF-α levels and to down-regulate neutrophil activation, probably by increasing intracellular cyclic AMP (27). We have previously shown that PTX protects rats from lung injury induced by ventilation with a high tidal volume (15).…”

Section: Discussionmentioning

confidence: 99%

Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

Oliveira-Júnior

Brunialti

Koh

et al. 2006

Braz J Med Biol Res

View full text Add to dashboard Cite

Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO 2 and high PaCO 2 , and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA) production assessed in bronchoalveolar lavage) in a sepsis model consisting of intraperitoneal (ip) injection of Escherichia coli and the protective effects of pentoxifylline (PTX). Male Wistar rats (weighing between 270 and 350 g) were injected ip with 10 7 or 10 9 CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group). PaO 2 , PaCO 2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group) and the animals were observed for 6 h. Injection of 10 7 or 10 9 CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P < 0.05) cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P < 0.05) in the septic groups compared to control. A higher tumor necrosis factor-alpha (P < 0.05) concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P < 0.05) most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions. Correspondence

show abstract

Pentoxifylline inhibits lipopolysaccharide-induced serum tumor necrosis factor and mortality

Cited by 85 publications

References 16 publications

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro

Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

Contact Info

Product

Resources

About