The effect of human complement C3 protein applied at different times in treatment of polymicrobial sepsis

This study was designed to investigate the effect of exogenous complement C3 administration on outcomes of sepsis and identify an optimal time for this therapy.

Colon ascendens stent peritonitis (CASP) was performed to induce sepsis in C57BL/6 mice, with sham-operated mice as control. Human purified C3 (HuC3, 1 mg) was administered via intraperitoneal injection, with 200 µl phosphate-buffered saline as control. Mice were categorized by the initiation time of HuC3 treatment. Survival, bacterial burden, vital organ damages, histology changes, and expression of C3 were compared between the groups.

CASP-induced sepsis caused rapid complement C3 depletion and severe organ damage. Vital organs suffered from substantial bacterial loads. Exogenous C3 applied in the early stage of sepsis was associated with attenuated organ injuries, enhanced bacterial clearance, and improved survival. Exogenous C3 application promoted the synthesis of C3 in the early stage of sepsis. It appears that 6 h post-CASP surgery is the optimal time for HuC3 therapy.

The study confirmed the positive effect of exogenous C3 on treatment of polymicrobial sepsis. C3 supplementation prior to the appearance of complement depletion could protect vital organs and its administration in the early stage of sepsis should be encouraged .