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Updated: Dec 7, 2025
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
CD123 thioaptamer protects against sepsis via the blockade between IL-3/CD123 in a cecal ligation and puncture rat
Jiangang Zhao1, Meng Wang2, Ying Yang3
1Department of Neonatal, Xi'an Children's Hospital, Xi'an, Shaanxi, People's Republic of China.
Insights
A novel thioaptamer, SS30, shows promise in treating sepsis by inhibiting the IL-3/CD123 interaction. This sepsis treatment reduced mortality in rats by down-regulating the JAK2/STAT5 pathway and lowering harmful cytokines.
Area of Science:
- Biomedical research
- Immunology
- Pharmacology
Background:
- Sepsis is a leading cause of death in ICUs, particularly dangerous for pediatric patients.
- Interleukin-3 (IL-3) plays a critical role in sepsis progression; inhibiting IL-3 may alleviate the condition.
- A previously developed CD123 aptamer successfully inhibited the CD123-IL-3 interaction.
Purpose of the Study:
- To investigate the protective effects of the thioaptamer SS30 against sepsis using a cecal ligation and puncture (CLP) rat model.
- To evaluate SS30's efficacy in blocking the IL-3/CD123 recognition pathway.
- To compare SS30's protective ability against a CD123 antibody.
Main Methods:
- Established a CLP rat model to simulate sepsis conditions.
- Administered CD123 thioaptamer SS30 and a CD123 antibody to block IL-3/CD123 interaction.
- Monitored physiological parameters (body weight, temperature, blood gas, MAP) and serum cytokines (lactate, TNF-α, IL-1β, IL-6).
- Assessed JAK2 and STAT5 protein expression using flow cytometry.
Main Results:
- Rats treated with SS30 or CD123 antibody showed reduced levels of pro-inflammatory cytokines and improved physiological markers (temperature, MAP, PO2/FiO2, ETCO2) compared to the CLP group.
- SS30 treatment led to decreased expression of phosphorylated JAK2 and STAT5.
- The thioaptamer SS30 demonstrated superior protective effects compared to the CD123 antibody, increasing survival rates.
Conclusions:
- CD123 thioaptamer SS30 effectively reduces sepsis mortality in a CLP rat model.
- SS30 functions by down-regulating the phosphorylated JAK2/STAT5 signaling pathway.
- SS30 mitigates sepsis by reducing key serum cytokines involved in the inflammatory process.
Abstract:
Sepsis is one of the most common causes of death in ICU and especially is a harmful and a life-threatened disease to pediatrics in the world. It has been demonstrated that IL-3 plays an essential role in the processing of sepsis and the inhibition of IL-3 may alleviate sepsis progress. In our previous study, we selected a novel CD123 aptamer successfully which could inhibit the interaction of CD123 and IL-3. The aim of this study is to explore the protection ability of the first thioaptamer SS30 against sepsis in a cecal ligation and puncture (CLP) rat model. Serum IL-3 level of sepsis patients was assessed by ELISA. CLP rat model was applied in all experimental groups. CD123 thioaptamer SS30 and CD123 antibody were used to block the recognition between IL-3 and CD123. Body weight, temperature, blood gas, MAP, and serum cytokines of four grouped rats were assessed. Flow cytometry was utilized to evaluate JAK2 and STAT5 proteins. After the administration of SS30 or CD123 antibody, the rats in SS30 and CD123 antibody group had lower cytokines values(lactate, TNF-α, IL-1β, and IL-6), whereas exhibited higher value of core temperature, MAP, PO2/FiO2, and ETCO2 than those in the CLP group. The expression level of phosphorylated JAK2 and STAT5 was declined and the survival rate of rats was increased. In addition, the protection ability of SS30 was better than CD123 antibody. Therefore, CD123 thioaptamer SS30 could reduce mortality by down-regulating the phosphorylated JAK2/STAT5 signaling pathway, and reduce serum cytokines which involving in sepsis development in CLP rat model.
