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Journal article
Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis
Scientific reports, v 9(1), pp 2904-2904
27 Feb 2019
PMID: 30814582
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 mu M) 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-alpha, 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.
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Details
- Title
- Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis
- Creators
- Pragnya Das - Drexel UniversitySantosh K. Panda - Washington University in St. LouisBeamon Agarwal - GenomeRxUS, 1250 Providence Rd, Secane, PA, 19018, USA.Sumita Behera - University of Cincinnati Medical CenterSyed M. Ali - Jamia Millia Islamia, Dept Biotechnol, New Delhi 110025, IndiaMark E. Pulse - University of North Texas Health Science CenterJoseph S. Solomkin - University of Cincinnati Medical CenterSteven M. Opal - Brown UniversityVineet Bhandari - Drexel UniversitySuchismita Acharya - University of North Texas Health Science Center
- Publication Details
- Scientific reports, v 9(1), pp 2904-2904
- Publisher
- Springer Nature
- Number of pages
- 12
- Grant note
- R43AI129164-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000459799800053
- Scopus ID
- 2-s2.0-85062279047
- Other Identifier
- 991019167418504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology