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Anti-inflammatory cytokines such as IL-10 inhibit inflammation and enhance tissue healing. Here, we report a novel approach to treat septicemia associated with intra-abdominal infection in a murine model by delicately balancing pro- and anti-inflammatory cytokines. A novel oligosaccharide compound<jats:bold>AVR-25<\/jats:bold>selectively binds to the TLR4 protein (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.15\u2009\u00b5M) in human peripheral blood monocytes and stimulates IL-10 production. Following the cecal ligation and puncture (CLP) procedure, intravenous dosing of<jats:bold>AVR-25<\/jats:bold>(10\u2009mg\/kg, 6\u201312\u2009h post-CLP) alone and in combination with antibiotic<jats:bold>imipenem<\/jats:bold>protected both young adult (10\u201312 week old) and aged (16\u201318 month old) mice against polymicrobial infection, organ dysfunction, and death. Proinflammatory cytokines (TNF-\u03b1, MIP-1, i-NOS) were decreased significantly and restoration of tissue damage was observed in all organs. A decrease in serum C-reactive protein (CRP) and bacterial colony forming unit (CFU) confirmed improved bacterial clearance. Together, these findings demonstrate the therapeutic ability of<jats:bold>AVR-25<\/jats:bold>to mitigate the storm of inflammation and minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis.<\/jats:p>","DOI":"10.1038\/s41598-019-38731-3","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T11:27:43Z","timestamp":1551266863000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis"],"prefix":"10.1038","volume":"9","author":[{"given":"Pragnya","family":"Das","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh K.","family":"Panda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beamon","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Behera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7832","authenticated-orcid":false,"given":"Syed M.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Pulse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph S.","family":"Solomkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Opal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-6636","authenticated-orcid":false,"given":"Vineet","family":"Bhandari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchismita","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"issue":"12","key":"38731_CR1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.2165\/00019053-200422120-00003","volume":"22","author":"H Burchardi","year":"2004","unstructured":"Burchardi, H. & Schneider, H. 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Mutagenesis 19, 245\u2013250 (2004).","journal-title":"Mutagenesis"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-38731-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-38731-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-38731-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T23:53:11Z","timestamp":1694649191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-38731-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,27]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["38731"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-38731-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,27]]},"assertion":[{"value":"17 September 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The work done by M.E.P. and V.B. was funded by AyuVis Research as subaward from the NIH grant. S.M.O. and S.K.P. received compensation from AyuVis as a member of the scientific advisory board and as consultant, respectively. S.B. received compensation as a contract employee from AyuVis Research. No competing financial or non-financial competing interest is noted for S.A., J.S.S., and B.A.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"2904"}}