Changes in plasma HDL and its subcomponents HDL2b and HDL3 regulate inflammatory response by modulating SOCS1 signaling to affect severity degree and prognosis of sepsis.

Abstract

To explore if SOCS1 is regulated by plasma HDL and its subcomponents HDL2b and HDL3 to affect inflammatory reaction then to influence the severity degree and prognosis of sepsis. One hundred sepsis patients in ICU and 85 normal control persons from October 2018 to October 2019 in our hospital were enrolled. Adult male C57BL/6 mice were used to establish sepsis model by CLP method. HDL, CRP, and WBC count of human were measured using an auto-analyzer. Plasma HDL, IL-1β, and TNF-α proteins levels of mice were measured with ELISA. Microfluidic chip was used for plasma HDL2b and HDL3 detections. SOCS1 in liver and spleen of mice were measured by qRT-PCR. The relationship between plasma HDL//HDL2b and inflammatory indices/SOCS1 in liver/spleen was analyzed with spearman correlation coefficient method. The sepsis patients/mice were divided into non-survival and survival groups. The sepsis patients were divided into severe and mild sepsis patients based on the SOFA score or divided into high and low score groups according to the APACHE II score. The sepsis mice were divided into high and low score group based on the modified sepsis severity score criterion. Plasma HDL and HDL2b levels were significantly declined (P<0.01), while HDL3 was normal in both sepsis patients and mice (P>0.05). Plasma HDL and HDL2b were negatively associated with the serum CRP concentration and positively correlated with the prognosis and severity in sepsis patients (P<0.05). Moreover, the downregulated plasma HDL but not HDL2b was negatively related to increased SOCS1 mRNA levels in liver and spleen of mice, which were positively connected with TNF-α and IL-1β protein levels (P<0.05). Plasma HDL is downregulated in sepsis, which may facilitate inflammatory reaction then activate the SOCS1 signaling to regulate the severity and affect prognosis of sepsis. The decline of plasma HDL2b content could aggravate the severity and poor prognosis of sepsis through facilitating inflammatory reaction. The plasma HDL3 is not involved in sepsis. The more and further explorations may be needed.