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Anti‐Inflammatory Effects of Famotidine
Author(s) -
George Sam,
Thompson Dane,
Tynan Aisling,
Silverman Harold,
Li Jian Hua,
Chang Eric,
Andersson Ulf,
Chavan Sangeeta,
Tracey Kevin,
Yang Huan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04287
Subject(s) - famotidine , medicine , lipopolysaccharide , antagonist , tumor necrosis factor alpha , histamine , sepsis , cytokine , intraperitoneal injection , peripheral blood mononuclear cell , pharmacology , endocrinology , immunology , receptor , chemistry , biochemistry , in vitro
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.