Modulation of TNFα and IL-6 in a peritonitis model using pentoxifylline

Refsum, S.E.; Halliday, M. I.; Campbell, Gareth; McCaigue, M. D.; Boston, V. E.

doi:10.1016/s0022-3468(96)90413-3

Cited by 15 publications

(7 citation statements)

References 12 publications

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“…The metalloproteinase enzyme TACE/ADAM17 is an ␣-secretase that is known to play an important role in the cleavage of several membrane receptors, such as those for TNF␣, IL-6, and EGF (27). The mechanism by which TACE recognizes and cleaves specific membrane receptors is not fully understood but may be cell type-and model-dependent (27).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism by which TACE recognizes and cleaves specific membrane receptors is not fully understood but may be cell type-and model-dependent (27). It has been previously shown that TACE glycosylation and phosphorylation may be important in either the localization of TACE to the membrane (30) or its activation (51)(52)(53)(54).…”

Section: Discussionmentioning

confidence: 99%

“…Cleavage of TNFR1 by TACE leads to the release of soluble TNFR1 (sTNFR1), which not only reduces the number of receptors available on the outside of hepatocytes but also binds to circulating TNF␣ to prevent its inflammatory effects (20 -23). The formation of sTNFR1 is a constitutive process (24 -26) but is increased under inflammatory disease conditions or after stimulation with cytokines TNF␣, interleukin (IL)-1␤, and IL-10 as well as with lipopolysaccharide (LPS; endotoxin) (27)(28)(29).…”

Section: Tumor Necrosis Factor (Tnf)mentioning

confidence: 99%

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A Role for cGMP in Inducible Nitric-oxide Synthase (iNOS)-induced Tumor Necrosis Factor (TNF) α-converting Enzyme (TACE/ADAM17) Activation, Translocation, and TNF Receptor 1 (TNFR1) Shedding in Hepatocytes

Chanthaphavong

Loughran

Lee

et al. 2012

Journal of Biological Chemistry

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Background: iNOS/NO blocks TNF␣-induced apoptosis by cGMP-dependent and cGMP-independent mechanisms in hepatocytes. Result: TLR4-dependent iNOS expression in hepatocytes leads to NO/cGMP/PKG-dependent TACE/ADAM17 and iRhom2 phosphorylation and interaction, TACE/ADAM17 activation/surface translocation, and TNFR1 shedding. Conclusion: iNOS expression leads to rapid TNFR1 shedding through NO/cGMP/PKG-dependent translocation and activation of TACE/ADAM17. Significance: This novel mechanism for iNOS/NO/cGMP-induced TACE activation and translocation may limit TNF␣-mediated signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Tumor Necrosis Factor (Tnf)mentioning

confidence: 99%

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A Role for cGMP in Inducible Nitric-oxide Synthase (iNOS)-induced Tumor Necrosis Factor (TNF) α-converting Enzyme (TACE/ADAM17) Activation, Translocation, and TNF Receptor 1 (TNFR1) Shedding in Hepatocytes

Chanthaphavong

Loughran

Lee

et al. 2012

Journal of Biological Chemistry

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“…Even though steroids are an established component of the pharmacological management of severe P. carinii pneumonia, the mechanisms by which these drugs reduce mortality and improve outcomes in P. carinii pneumonia have not been fully elucidated. We postulate that stimulation of macrophage TNF-␣ release by active components of the organism's cell wall should be inhibited by the potent glucocorticoid dexamethasone, or by the drug pentoxifylline, another agent that can inhibit mononuclear cell TNF-␣ release (21)(22)(23).…”

mentioning

confidence: 99%

Isolated Pneumocystis carinii Cell Wall Glucan Provokes Lower Respiratory Tract Inflammatory Responses

Vassallo¹,

Standing²,

Limper

2000

The Journal of Immunology

141

153

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Macrophage-induced lung inflammation contributes substantially to respiratory failure during Pneumocystis carinii pneumonia. We isolated a P. carinii cell wall fraction rich in glucan carbohydrate, which potently induces TNF-α and macrophage-inflammatory protein-2 generation from alveolar macrophages. Instillation of this purified P. carinii carbohydrate cell wall fraction into healthy rodents is accompanied by substantial increases in whole lung TNF-α generation and is associated with neutrophilic infiltration of the lungs. Digestion of the P. carinii cell wall isolate with zymolyase, a preparation containing predominantly β-1,3 glucanase, substantially reduces the ability of this P. carinii cell wall fraction to activate alveolar macrophages, thus suggesting that β-glucan components of the P. carinii cell wall largely mediate TNF-α release. Furthermore, the soluble carbohydrate β-glucan receptor antagonists laminariheptaose and laminarin also substantially reduce the ability of the P. carinii cell wall isolate to stimulate macrophage-inflammatory activation. In contrast, soluble α-mannan, a preparation that antagonizes macrophage mannose receptors, had minimal effect on TNF-α release induced by the P. carinii cell wall fraction. P. carinii β-glucan-induced TNF-α release from alveolar macrophages was also inhibited by both dexamethasone and pentoxifylline, two pharmacological agents with potential activity in controlling P. carinii-induced lung inflammation. These data demonstrate that P. carinii β-glucan cell wall components can directly stimulate alveolar macrophages to release proinflammatory cytokines mainly through interaction with cognate β-glucan receptors on the phagocyte.

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“…Pentoxifylline has been one of the most common nonspecific immunomodulator drugs reported in basic research. Pentoxifylline exerts a specific action on TNF-a synthesis and it is known to inhibit phosphodiesterase and signal transcription of TNF-a and IL-6 [84], but it has clinical relevance only in the early phases of secondary peritonitis (6 h after the onset of bacterial contamination). On models of chronic secondary peritonitis, low-dose (but not highdose) pentoxifylline administration reduced the production of IL-6 in liver and gut, improving survival of treated animals.…”

Section: Nonspecific Immunomodulatorsmentioning

confidence: 99%

Cytokine Responses in Secondary Peritonitis

Emparan¹,

Senninger²

2000

Visc Med

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The onset of local and systemic inflammatory effects in secondary peritonitis is usually closely related to the presence of many inflammatory mediators such as cytokines. The main purpose of this paper is to review the mechanisms induced by secondary peritonitis related to the production of cytokines, to determine their role in the onset of local inflammatory responses and in the onset of systemic inflammatory responses leading to multiple organ failure. We also review the immunomodulatory effects induced by cytokine production and their counteraction. Finally we analyze the potential therapeutic effects of cytokine-related drugs and their role in the management of patients with secondary peritonitis and systemic inflammatory response syndrome. In this regard the following substances are important: nonspecific immunomodulators, anti-cytokine antibodies, and inhibitors of the cytokine effect and of adhesion molecules.

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Modulation of TNFα and IL-6 in a peritonitis model using pentoxifylline

Cited by 15 publications

References 12 publications

A Role for cGMP in Inducible Nitric-oxide Synthase (iNOS)-induced Tumor Necrosis Factor (TNF) α-converting Enzyme (TACE/ADAM17) Activation, Translocation, and TNF Receptor 1 (TNFR1) Shedding in Hepatocytes

A Role for cGMP in Inducible Nitric-oxide Synthase (iNOS)-induced Tumor Necrosis Factor (TNF) α-converting Enzyme (TACE/ADAM17) Activation, Translocation, and TNF Receptor 1 (TNFR1) Shedding in Hepatocytes

Isolated Pneumocystis carinii Cell Wall Glucan Provokes Lower Respiratory Tract Inflammatory Responses

Cytokine Responses in Secondary Peritonitis

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