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Updated: Jun 28, 2026
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
Christopher C Moore1, Edward N Martin, Grace H Lee
1Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Box 801342, Charlottesville, VA 22908, USA. ccm5u@virginia.edu
Background:
The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.
Methods:
Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A 2A AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days.
Results:
There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-alpha, MIP-1 alpha, MCP-1, IFN-gamma, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01).
Conclusion:
Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.
Insights
The A2A adenosine receptor (AR) agonist ATL313 significantly improved survival in experimental sepsis models, reducing inflammatory markers and increasing beneficial cytokines. Further research is needed to explore its clinical use in sepsis treatment.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Sepsis pathophysiology involves early systemic inflammation.
- Investigating molecular and cellular responses in experimental sepsis is crucial.
- Adenosine receptors play a role in modulating inflammatory responses.
Purpose of the Study:
- To evaluate the efficacy of an A2A AR agonist (ATL313) in experimental sepsis models.
- To assess the impact of ATL313 on survival, inflammatory markers, and immune cell responses.
- To determine the potential of ATL313 as a novel therapeutic agent for sepsis.
Main Methods:
- Sepsis induced in mice via bacterial inoculation (E. coli, S. aureus) or LPS administration.
- Treatment with A2A AR agonist (ATL313) or placebo (PBS), with or without antibiotics.
- Measurement of serum cytokines and chemokines at various time points.
- Survival studies conducted over 7 days.
Main Results:
- ATL313 significantly improved survival in bacterial sepsis and endotoxic shock models.
- ATL313 treatment decreased pro-inflammatory cytokines (TNF-alpha, MIP-1 alpha, MCP-1, IFN-gamma, IL-17) and increased IL-10.
- Increased circulating white blood cell counts observed in ATL313 treated animals.
Conclusions:
- ATL313 demonstrates significant therapeutic potential in experimental sepsis.
- The A2A AR agonist modulates key inflammatory mediators and improves survival outcomes.
- Further clinical studies are warranted to establish the utility of ATL313 for sepsis treatment.