摘要
Abstract
Objective:The mononuclear phagocyte system participates in both innate and adaptive immune responses and exhibits remarkable plasticity,playing important roles in inflammatory response and tissue repair in liver injury.This study aims to investigate the correlation between the elevation of peripheral blood monocyte percentage in patients with drug-induced liver injury(DILI)and the severity of the disease,as well as to detect the levels of peripheral blood M1 and M2 subtypes.
Methods:Clinical data were collected from 170 patients with DILI[divided into a mild to moderate group(n=49)and a severe and above group(n=121)],and 100 healthy individuals(a control group).Clinical parameters among the 3 groups were compared.Correlation analyses were conducted between the monocyte percentage,lymphocyte percentage,ratio of lymphocyte to monocyte(LMR),and clinical parameters of liver function in DILI patients.Additionally,fasting elbow venous blood samples were collected from 10 healthy individuals and 13 DILI patients upon admission(before treatment)and after 2 weeks of treatment.Flow cytometry was employed to detect the expression of CD86(M1 monocytes)and CD163(M2 monocytes)on the surface of peripheral blood monocytes.
Result:The percentage of monocytes in DILI patients was positively correlated with the level of total bilirubin(TBil)(r=0.512,P<0.01).LMR and lymphocyte percentage were negatively correlated with TBil levels(r=-0.499,r=-0.259,both P<0.01).Flow cytometry results demonstrated a significant increase in M1 monocytes(P<0.001)and a decrease in M2 monocytes(P=0.036),leading to a decrease M2/M1 ratio(P=0.011)in peripheral blood of the DILI group compared to the control group.In the DILI patients,with the improvement of liver function,the trend of changes in M1 and M2 monocytes reversed,leading to an increase in the M2/M1 ratio(P=0.034).
Conclusion:The increase of peripheral blood monocytes percentage and the decrease in LMR are closely associated with the severity of liver injury in DILI patients.Furthermore,during the progression of liver injury,the increase in M1 monocytes predominates,while with the improvement of liver function,M2 monocytes gradually recover.Therefore,targeting the polarization of monocytes/macrophages towards M1 or M2 phenotypes may serve as a novel therapeutic strategy for DILI in the future.关键词
药物性肝损伤/单核巨噬细胞系统/M1/M2/极化Key words
drug-induced liver injury/mononuclear phagocyte system/M1/M2/polarization
