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IMP can also serve as an extracellular signaling molecule, and can regulate diverse processes such as taste sensation, neutrophil function, and ischemia\u2010reperfusion injury. How IMP regulates inflammation induced by bacterial products or bacteria is unknown. In this study, we demonstrate that IMP suppressed tumor necrosis factor (TNF)\u2010\u03b1 production and augmented IL\u201010 production in endotoxemic mice. IMP exerted its effects through metabolism to inosine, as IMP only suppressed TNF\u2010\u03b1 following its CD73\u2010mediated degradation to inosine in lipopolysaccharide\u2010activated macrophages. Studies with gene targeted mice and pharmacological antagonism indicated that A\n                    <jats:sub>2A<\/jats:sub>\n                    , A\n                    <jats:sub>2B,<\/jats:sub>\n                    and A\n                    <jats:sub>3<\/jats:sub>\n                    adenosine receptors are not required for the inosine suppression of TNF\u2010\u03b1 production. The inosine suppression of TNF\u2010\u03b1 production did not require its metabolism to hypoxanthine through purine nucleoside phosphorylase or its uptake into cells through concentrative nucleoside transporters indicating a role for alternative metabolic\/uptake pathways. Inosine augmented IL\u2010\u03b2 production by macrophages in which inflammasome was activated by lipopolysaccharide and ATP. In contrast to its effects in endotoxemia, IMP failed to affect the inflammatory response to abdominal sepsis and pneumonia. We conclude that extracellular IMP and inosine differentially regulate the inflammatory response.\n                  <\/jats:p>","DOI":"10.1096\/fj.202100862r","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T15:10:24Z","timestamp":1633014624000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Inosine monophosphate and inosine differentially regulate endotoxemia and bacterial sepsis"],"prefix":"10.1096","volume":"35","author":[{"given":"Marianna","family":"Lov\u00e1szi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Columbia University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n H.","family":"N\u00e9meth","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Columbia University New York New York USA"},{"name":"Department of Surgery Morristown Medical Center Morristown New 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