Disease relevance of TNFA

• Moreover, the finding that in this mild model anti-TNF specifically inhibited fibrinolysis suggests that treatment with anti-TNF potentially may enhance the tendency towards microvascular thrombosis in sepsis [1].
• To assess the intermediate role of TNF in specific systemic inflammatory responses known to contribute to tissue injury in endotoxemia, eight healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg) [1].
• These results suggest that TNF is not the common mediator of systemic inflammatory changes in low-grade endotoxemia [1].
• Neutrophilia and lymphopenia were not affected by anti-TNF, whereas neutrophil degranulation, as measured by the plasma concentrations of elastase-alpha 1-antitrypsin complexes, was only slightly reduced (peak levels after endotoxin alone 31.0 +/- 3.4 ng/mL, versus 25.5 +/- 3.4 ng/mL after endotoxin with anti-TNF; P < .05) [1].
• Effect of linomide on gut immune cell distribution and on TNF-alpha in plasma and ascites: an experimental study in the septic rat [2].

High impact information on TNFA

• Tumor necrosis factor (TNF) is considered to be a pivotal mediator of endotoxin-induced lethality [1].
• Pentoxifylline inhibits various neutrophil functions in vitro, and attenuates endotoxin-induced production of TNF in both in vitro and in vivo models [3].
• Pentoxifylline also inhibited the endotoxin-induced release of TNF (271 +/- 26 vs 55 +/- 23 pg/ml at t = 1.5 h; p < 0.05) and IL-6 (225 +/- 42 vs 73 +/- 25 pg/ml at t = 2 h; p < 0.05) [3].
• The endotoxin-induced effects on bronchoalveolar fibrinolysis could be blocked by the simultaneous administration of anti- TNF-alpha antibodies [4].
• Sepsis caused increased concentrations of TNF-alpha in portal blood and ascites 3 h from CLP induction [2].

Chemical compound and disease context of TNFA

• We conclude that pentoxifylline attenuates neutrophil activation in endotoxemia in chimpanzees, probably in part by inhibiting the release of TNF [3].

Anatomical context of TNFA

• The aim of this study was to evaluate if the immunomodulator Linomide influenced the immune cell distribution in the small intestinal mucosa in sepsis and, furthermore, if these changes coincide with changes in the concentration of tumor necrosis factor-alpha (TNF-alpha) in plasma or ascites [2].

Analytical, diagnostic and therapeutic context of TNFA

• In four of these animals the administration of endotoxin was followed immediately by a bolus intravenous injection of an anti-TNF monoclonal antibody (15 mg/kg) [1].

References