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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Pragnya Das, Santosh K. Panda, Beamon Agarwal, Sumita Behera, Syed M. Ali, Mark E. Pulse, Joseph S. Solomkin, Steven M. Opal, Vineet Bhandari, Suchismita 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 minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis. More... »

PAGES

2904

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-38731-3

DOI

http://dx.doi.org/10.1038/s41598-019-38731-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112395295

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30814582


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RDF/XML is a standard XML format for linked data.

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