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

Scientific Reports
Pragnya DasSuchismita Acharya

Abstract

In 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-α, 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 minim...Continue Reading

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Citations

Jun 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saleh A AlmatroodiArshad Husain Rahmani
Sep 26, 2019·Frontiers in Bioengineering and Biotechnology·Diana Larisa RomanAdriana Isvoran
Mar 29, 2021·The International Journal of Biochemistry & Cell Biology·Haiyan ChenZongfang Li

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Methods Mentioned

BETA
ELISA
PMA

Software Mentioned

GraphPad Prism
GraphPad

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