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The FASEB Journal ; 35(S1), 2021.
Article in English | Wiley | ID: covidwho-1234045


The COVID-19 pandemic in the U.S. currently exceeds 21.1 million cases and 350,000 deaths. Consumption of famotidine, a histamine H2 receptor antagonist widely used to treat acid reflux and gastritis, is associated with improved survival and attenuated COVID-19 disease severity (Mather JF et al. Am J Gastroenterol. 115:1617,2020;Freedberg DE, et al. Gastroenterology 159: 1129, 2020;Janowitz T et al. Gut, 69:1592, 2020). However, the mode of action for these beneficial effects is unknown. Here we studied famotidine in mice exposed to bacterial endotoxin (lipopolysaccharide, LPS). LPS (6 mg/kg) was administered intraperitoneally in male C57BL/6 mice followed by intraperitoneal injection of famotidine (100 µg/mouse) or vehicle (PBS) twice daily for 3 days. Two-week survival was 100% in the famotidine-treated group vs. 70% in the PBS-control group (n=30/group, p < 0.05). Furthermore, famotidine administration significantly reduced serum and splenic TNF levels and serum IL-6 levels in the endotoxemic mice (p<0.05, famotidine vs. PBS). Human peripheral blood mononuclear cells co-cultured with famotidine and LPS also express significantly reduced amounts of pro-inflammatory cytokines (TNF, IL-6, HMGB1, IP-10, GM-CSF). Together these results indicate famotidine inhibits endotoxin induced cytokine storm and attenuates lethality in mice exposed to lethal endotoxemia.