Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis

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dc.creatorDas, Pragnya
dc.creatorPanda, Santosh K.
dc.creatorAgarwal, Beamon
dc.creatorBehera, Sumita
dc.creatorAli, Syed M.
dc.creatorPulse, Mark E.
dc.creatorSolomkin, Joseph S.
dc.creatorOpal, Steven M.
dc.creatorBhandari, Vineet
dc.creatorAcharya, Suchismita
dc.date.accessioned2022-08-18T18:32:06Z
dc.date.available2022-08-18T18:32:06Z
dc.date.issued2019-02-27
dc.description.abstractIn Gram-negative bacterial sepsis, production of excess pro-inflammatory cytokines results in hyperinflammation and tissue injury. 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 AVR-25 selectively binds to the TLR4 protein (IC50 = 0.15 µM) in human peripheral blood monocytes and stimulates IL-10 production. Following the cecal ligation and puncture (CLP) procedure, intravenous dosing of AVR-25 (10 mg/kg, 6-12 h post-CLP) alone and in combination with antibiotic imipenem protected both young adult (10-12 week old) and aged (16-18 month old) mice against polymicrobial infection, organ dysfunction, and death. Proinflammatory cytokines (TNF-ɑ, 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 AVR-25 to mitigate the storm of inflammation and minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis.
dc.description.sponsorshipWe are thankful to NIH R43AI129164-01 (SA) for the funding to AyuVis Research Inc.
dc.identifier.citationDas, P., Panda, S. K., Agarwal, B., Behera, S., Ali, S. M., Pulse, M. E., Solomkin, J. S., Opal, S. M., Bhandari, V., & Acharya, S. (2019). Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis. Scientific reports, 9(1), 2904. https://doi.org/10.1038/s41598-019-38731-3
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31590
dc.identifier.volume9
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-019-38731-3
dc.rights.holder© The Author(s) 2019
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshAging / physiology
dc.subject.meshAnimals
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal / therapeutic use
dc.subject.meshCecum / surgery
dc.subject.meshCells, Cultured
dc.subject.meshChitin / chemistry
dc.subject.meshChitin / therapeutic use
dc.subject.meshCytokines / metabolism
dc.subject.meshDisease Models, Animal
dc.subject.meshGram-Negative Bacterial Infections / complications
dc.subject.meshGram-Negative Bacterial Infections / drug therapy
dc.subject.meshHumans
dc.subject.meshInflammation Mediators / metabolism
dc.subject.meshIntraabdominal Infections / complications
dc.subject.meshIntraabdominal Infections / drug therapy
dc.subject.meshLeukocytes, Mononuclear / drug effects
dc.subject.meshLeukocytes, Mononuclear / physiology
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshOligosaccharides / chemistry
dc.subject.meshOligosaccharides / therapeutic use
dc.subject.meshSepsis / etiology
dc.subject.meshSepsis / prevention & control
dc.subject.meshToll-Like Receptor 4 / metabolism
dc.titleNovel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis
dc.typeArticle
dc.type.materialtext

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