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

- Our study is the first report systematically investigating the turning point and demonstrating Day 1 after the surgery is the turning point in mice CLP model.
- CLP mice were more sensitive to P. aeruginosa at the turning point than Sham mice. The ability to clear bacteria of CLP mice challenged with P. aeruginosa is lower at the turning point than that of Sham mice.
- The levels of pro-inflammatory and anti-inflammatory cytokines in CLP mice challenged with P. aeruginosa couldn't obviously increase at the turning point compared with Sham mice challenged with P. aeruginosa.
- The white blood cells, monocytes, and lymphocytes of CLP mice were much lower than those of Sham mice except basophile granulocytes and eosinophile granulocytes.

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 × 107, 5.0 × 106 and 1.0 × 106 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.