Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine...

Area of Science:

• Sepsis research
• Infectious disease immunology
• Coagulation and inflammation pathways

Background:

• Recombinant human activated protein C (APC) demonstrates anticoagulant and anti-inflammatory effects, improving survival in severe sepsis patients.
• Previous studies suggest early APC treatment yields better therapeutic responses in sepsis.
• While recombinant murine APC (rm-APC) reduced coagulation activation in a pneumococcal pneumonia mouse model, it did not affect inflammation.

Purpose of the Study:

• To investigate the impact of early recombinant murine activated protein C (rm-APC) treatment on coagulation and inflammation in a mouse model of pneumococcal pneumonia.

Main Methods:

• Mice were infected intranasally with Streptococcus pneumoniae.
• Treatment with rm-APC (125 μg) or vehicle was administered intraperitoneally 12 hours post-infection.
• Animals were sacrificed 20 hours later for analysis of bacterial load, coagulation markers (thrombin-antithrombin complexes, D-dimer), and inflammatory cytokines/chemokines in blood and lung tissue.

Main Results:

• Early rm-APC treatment significantly inhibited both pulmonary and systemic coagulation activation.
• Reduced levels of thrombin-antithrombin complexes and D-dimer were observed in rm-APC treated mice.
• rm-APC administration led to a significant decrease in numerous pro-inflammatory cytokines and chemokines within the lung tissue.

Conclusions:

• Early administration of rm-APC effectively inhibits systemic and pulmonary coagulation activation in pneumococcal pneumonia.
• rm-APC exerts significant anti-inflammatory effects in the lung when treatment is initiated early in the course of infection.
• These findings support the potential of early APC intervention for managing severe sepsis associated with pneumococcal pneumonia.