Protective potential of 2-chloroadenosine in Klebsiella pneumoniae B5055 induced sepsis in BALB/c mice

Background

The incidence of sepsis or systemic inflammatory response syndrome in both developing countries as well as in the developed countries is rising despite the extensive research in understanding the molecular basis of sepsis pathogenesis. Sepsis is currently treated with antibiotics along with various adjunctive therapies. However, current existing therapies do not provide much efficacy in terms of patient survival and development of multiorgan dysfunction during sepsis.

Methods

In the present study, we have developed the murine model of sepsis by placing Klebsiella pneumoniae B5055 entrapped in fibrin-thrombin clot in the peritoneal cavity of BALB/c mice. The mice were subsequently treated with adenosine analog 2-chloroadenosine (10 μg/kg/day intravenously). The efficacy of 2-chloroadenosine was investigated in terms of survival of animals and various inflammatory parameters (that is, malondiadehyde, myeloperoxidase, nitric oxide) in the lungs, liver and serum. Also the levels of proinflammatory cytokines (that is, TNFα and IL-1α) were determined.

Results

The 2-chloroadenosine treatment significantly improved the survival of animals over a period of 5 days and increased the survival of animals to 70% as compared with the control group where 100% mortality was observed. The 2-chloroadenosine treatment significantly (P < 0.05) decreased the production of TNFα, IL-1α and malondiadehyde, myeloperoxidase, and nitric oxide production in the serum, lung and liver of mice.

Conclusion

The 2-chloroadenosine protected the mice from sepsis by increasing their survival and by decreasing the production of inflammatory markers investigated in the study.