Portal infusion of tumor necrosis factor increases mortality in rats

Kahky, Michael P.; Daniel, Craig O.; Cruz, Anatolio B.; Gaskill, Harold V.

doi:10.1016/0022-4804(90)90252-w

Cited by 31 publications

(14 citation statements)

References 13 publications

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“…In addition, portal infusion of TNF-causes gastric and small intestinal damage in rats, with nearly total loss of the mucosa. 34 The present study has demonstrated that pioglitazone treatment inhibits the increase in the TNFconcentration as well as the expression of TNFmRNA in the intestinal mucosa after I-R. These findings support the hypothesis that pioglitazone attenuates I-Rinduced neutrophil accumulation by inhibiting the expression of TNF-.…”

Section: Discussionsupporting

confidence: 78%

Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-γ ligand, pioglitazone, in rats

et al. 2002

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Section: Discussionsupporting

confidence: 78%

Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-γ ligand, pioglitazone, in rats

et al. 2002

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“…TNF-α is a pro-inflammatory cytokine capable of up-regulating its own expression as well as the expressions of other genes pivotal to the inflammatory response. The production of TNF-α is generally thought to be harmful to the gastrointestinal system, because portal infusion of TNF-α causes gastric and small intestinal damage in rats, with a nearly total loss of mucosa (20), and TNF-α elicits epithelial barrier defects in colonic cell monolayers (21) and chemokine secretion from intestinal epithelial cells (22). Several reports have demonstrated the increases in intestinal TNF-α mRNA expression in this model of small intestinal injury (13).…”

Section: Discussionmentioning

confidence: 99%

Role of tumor necrosis factor-α in the pathogenesis of indomethacin-induced small intestinal injury in mice

Fukumoto

Naito

Takagi³

et al. 2011

Int J Mol Med

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Abstract. The pathogenesis of small intestinal damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is still unclear. For this reason, there is currently no therapeutic strategy for ameliorating such damage. On the other hand, molecular treatment strategies targeting tumor necrosis factor (TNF)-α exert beneficial effects on intestinal lesions in patients with inflammatory bowel disease (IBD). To clarify the participation of TNF-α in NSAID-induced small intestinal damage, we investigated the effects of indomethacin administration in mice with targeted deletion of the TNF-α gene. Indomethacin (10 mg/kg) was administered subcutaneously to male C57BL/6 (wild-type: WT) mice and TNF-α-deficient (TNF-α -/-) mice to induce small intestinal damage. The ulcer score, the tissue-associated myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and the expression of keratinocyte chemoattractant (KC) mRNA in the small intestinal mucosa were measured. In addition, we performed a TUNEL assay to evaluate indomethacininduced apoptosis of intestinal epithelial cells and measured the expression of caspase-3 protein and Bcl-2 mRNA. The ulcer score, MPO activity, and expression of KC mRNA were significantly increased after indomethacin administration. These increases were significantly inhibited in TNF-α -/-mice compared with WT mice. Apoptotic cells were observed by the TUNEL assay in the area of the ulcerative lesion, and they were significantly fewer in TNF-α -/-mice compared with WT mice. The expression of cleaved caspase-3 protein was induced by indomethacin administration, and significantly inhibited in TNF-α -/-mice compared with that of WT mice. The expression level of Bcl-2 mRNA in indomethacin-treated TNF-α -/-mice was significantly higher than that in WT mice. TNF-α plays an important role in the pathogenesis of indomethacin-induced small intestinal damage. These results suggest that TNF-α could become a new therapeutic target for NSAID-induced small intestinal damage.

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“…Some studies have revealed direct adverse effects of TNF-α on the gastrointestinal mucosa such as vasocongestion and tissue damage [17, 18]. Kahky et al [18]found that portal infusion of TNF-α caused gastric and …”

Section: Discussionmentioning

confidence: 99%

Pentoxifylline Accelerates Gastric Ulcer Healing in Rats: Roles of Tumor Necrosis Factor Alpha and Neutrophils during the Early Phase of Ulcer Healing

Shimizu

Watanabe²,

Arakawa³

et al. 2000

Digestion

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Background/Aims: Pentoxifylline has many anti-inflammatory properties including inhibition of production of tumor necrosis factor alpha (TNF-α). Although pentoxifylline prevents several types of gastric mucosal injury, the effect of this drug on ulcer healing is unknown. In this study, we examined the effect of pentoxifylline on healing of acetic acid induced gastric ulcers in rats. Methods: Rats with gastric ulcer received an intraperitoneal injection of 10 mg/kg pentoxifylline once daily for 14 days or for only the first 7 days or the last 7 days of the 14-day treatment period. Some rats were given antirat neutrophil antiserum intraperitoneally every other day. Ulcer size, myeloperoxidase activity, and concentration and location of TNF-α in ulcer tissue were assessed. Results: Administration of pentoxifylline for 14 days or for the first 7 days, but not for the last 7 days, of the 14-day treatment period accelerated ulcer healing. TNF-α was detected mainly in monocytes/macrophages and in some neutrophils at ulcer bases and margins. Pentoxifylline markedly decreased the concentration of TNF-α as well as the myeloperoxidase activity in ulcer tissue on days 2 and 4. Antirat neutrophil antiserum inhibited neutrophil infiltration into ulcer tissue and accelerated ulcer healing. Conclusion: Pentoxifylline accelerates healing of acetic acid induced gastric ulcer in rats. This effect may be due in part to reduction of neutrophil infiltration and inhibition of production of TNF-α by inflammatory cells. Early-phase inhibition of inflammatory response may accelerate ulcer healing.

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Portal infusion of tumor necrosis factor increases mortality in rats

Cited by 31 publications

References 13 publications

Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-γ ligand, pioglitazone, in rats

Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-γ ligand, pioglitazone, in rats

Role of tumor necrosis factor-α in the pathogenesis of indomethacin-induced small intestinal injury in mice

Pentoxifylline Accelerates Gastric Ulcer Healing in Rats: Roles of Tumor Necrosis Factor Alpha and Neutrophils during the Early Phase of Ulcer Healing

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