Anti‐Inflammatory Effects of Famotidine

Abstract

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\xa0days 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