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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 (IC 50 = 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.

Original languageEnglish
Article number2904
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

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Punctures
Ligation
Sepsis
Cytokines
Interleukin-10
Anti-Inflammatory Agents
Intraabdominal Infections
Inflammation
Imipenem
Wounds and Injuries
Coinfection
Oligosaccharides
C-Reactive Protein
Blood Proteins
Monocytes
Young Adult
Stem Cells
Anti-Bacterial Agents
chitohexaose
Therapeutics

Cite this

Das, Pragnya ; Panda, Santosh K. ; Agarwal, Beamon ; Behera, Sumita ; Ali, Syed M. ; Pulse, Mark E. ; Solomkin, Joseph S. ; Opal, Steven M. ; Bhandari, Vineet ; Acharya, Suchismita. / Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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Das, P, Panda, SK, Agarwal, B, Behera, S, Ali, SM, Pulse, ME, Solomkin, JS, Opal, SM, Bhandari, V & Acharya, S 2019, 'Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis', Scientific Reports, vol. 9, no. 1, 2904. https://doi.org/10.1038/s41598-019-38731-3

Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis. / Das, Pragnya; Panda, Santosh K.; Agarwal, Beamon; Behera, Sumita; Ali, Syed M.; Pulse, Mark E.; Solomkin, Joseph S.; Opal, Steven M.; Bhandari, Vineet; Acharya, Suchismita.

In: Scientific Reports, Vol. 9, No. 1, 2904, 01.12.2019.

Research output: Contribution to journalArticle

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