Study Of Expression Different Of Toll-like Receptor And It's Signal Pathway In CD14~+ Cell Between HLH And Sepsis Children

Objective:To compare the difference of the expression level of Toll like receptor(TLR)and its signaling pathway in mononuclear cells of children with hemophagocytic syndrome(HLH)and sepsis,explore the mechanism of Toll like receptor and its signaling pathway in the process of HLH and sepsis,to provide new ideas for the early differential diagnosis and more effective treatment of the disease.Methods:To collect peripheral blood of 18 cases of primary HLH children,18 cases of sepsis children and 18 cases of normal children.Useing flow cytometry to detect peripheral blood CD14~+cell membrane TLR 2,3,4,7,9 expression level;Useing RT-PCR method to detect the mRNA expression level of signaling molecules of TLRs signal pathway:MyD88,IRAK4,TRAF6,TRIF,TRAM,TBK1 and IRF3;Useing ELISA method to measure plasma level of IL-1?,IL-2,IL-6,IL-10,IL-12,IFN-?,IFN-?and TNF-?.Useing SPSS to compare the results of HLH group,sepsis group and healthy control group.Results:1.The expressions of TLR2,3 and 4 of CD14+cells in HLH and sepsis group were significantly higher than those of the control group(P<0.01),especially markedly increased in TLR2,but there was no significant difference between HLH and sepsis group(P>0.05).The expression of TLR7 in HLH group was significantly higher than that in the sepsis and the control group(P<0.05),but there was no significant increase in the sepsis group(P>0.05).2.MyD88 pathway:the expression of MyD88,IRAK4 and TRAF6 in HLH group were significantly higher than those in the control group(P<0.05).The expression of MyD88 in the sepsis group was significantly higher than that in the HLH group and the healthy control group(P<0.05),but the expression of TRAF6 in the sepsis group was lower than that in the other two group(P<0.05).TRIF pathway:the expression of TRAM in HLH group was significantly lower than the control group(P<0.05).Although the expression of TRIF,TBK1 and IRF3 group were higher than that of the healthy group,there was no statistial significance(P>0.05).The TRIF,TBK1,IRF3 in the sepsis group was significantly lower than that of HLH group and control group,with statistical significance.(P<0.05).3.The levels of IL-1?,IL-2,IL-10,IL-12,INF-?and TNF-?in plasma of the HLH and the sepsis group were significantly higher than control group(P<0.05),and IL-10,IL-12 and INF-?in the HLH group were higher than sepsis group(P<0.05),and the IL-1 and IL-6 in the sepsis group were significantly higher than the HLH group;The level of TNF-?in HLH and sepsis group was higher than that of normal control group(P<0.05),but there was no statistical significance between two groups of HLH and sepsis(P>0.05).The level of IFN-?increased in HLH and sepsis group,there was no significant difference compared with control group(P>0.05).Conclusion:1.TLR2,3 and 4 are possible involved in the immune response of HLH and sepsis,TLR7 may be involved in the occurrence of HLH.2.HLH is different from sepsis in thepathogenesis.The CD14~+cells did may be not play a leading role in the high inflammatory response;the MyD88 pathway in the TLR4 signaling pathway of CD14+cells in HLH group was activated and the TRIF pathway was limited,it is a possible important cause of immune imbalance in HLH.3.Cytokine levels showed that IL-1?,IL-6,IL-10,IL-12 and INF-?can be used as a means of differential diagnosis in clinical trials.