Systematic investigation on the turning point of over-inflammation to immunosuppression in CLP mice model and their characteristics

Abstract Immunosuppression is involved in refractory innate and adaptive immune responses and is considered to be the predominant driving force for mortality in sepsis. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study, but the turning point of over-inflammation to immunosuppression was reported differently. Herein, systematic investigation on the turning point of over-inflammation to immunosuppression in CLP mice model was carried out. The results showed only the mortality of mice challenged with of Pseudomonas aeruginosa on Day 1 not other days after the surgery was higher than that of other mice with Sham surgery, suggesting Day 1 after the CLP surgery might be the turning point. There was very low mortality even without death in Sham mice but the mortality was 80% after mice were challenged with 2.5 × 10 7 , 5.0 × 10 6 and 1.0 × 10 6  CFU/10 g of Pseudomonas aeruginosa , further demonstrating Day 1 after the CLP surgery was the turning point. And, CLP mice presented low levels of pro-inflammatory and anti-inflammatory cytokines, and high bacterial loads on Day 1. Additionally, the amounts and proportion of blood cells and monocytes significantly changed, too. In conclusion, Day 1 after the CLP surgery was the turning point of over-inflammation to immunosuppression, and low levels of cytokines and high bacterial loads were the characteristics of this model on Day 1, which is significant for pharmacological investigation on sepsis.