Attribution 4.0 International (CC BY 4.0)2022-08-182022-08-182019-02-27Das, 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/s41598-019-38731-32045-2322https://hdl.handle.net/20.500.12503/31590In 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.http://creativecommons.org/licenses/by/4.0/Aging / physiologyAnimalsAnti-Inflammatory Agents, Non-Steroidal / therapeutic useCecum / surgeryCells, CulturedChitin / chemistryChitin / therapeutic useCytokines / metabolismDisease Models, AnimalGram-Negative Bacterial Infections / complicationsGram-Negative Bacterial Infections / drug therapyHumansInflammation Mediators / metabolismIntraabdominal Infections / complicationsIntraabdominal Infections / drug therapyLeukocytes, Mononuclear / drug effectsLeukocytes, Mononuclear / physiologyMiceMice, Inbred C57BLOligosaccharides / chemistryOligosaccharides / therapeutic useSepsis / etiologySepsis / prevention & controlToll-Like Receptor 4 / metabolismArticle© The Author(s) 201991