Changes of TLRs signaling pathways in peripheral blood mononuclear cells of patients with severe septic shock
OBJECTIVE To explore the changes of Toll-like receptors(TLRs)signaling pathways and cellular im-mune inflammatory factors in peripheral blood mononuclear cells(PBMCs)of the patients with severe septic shock.METHODS A total of 101 patients with severe septic shock who were treated in Wuhan No.1 Hospital from Jan 2017 to Jan 2021 were assigned as the study group and were divided into the death group with 33 cases and the survival group with 68 cases according to the treatment outcomes within 28 days after the admission to intensive care unit(ICU),meanwhile,120 healthy people who received physical examination were chosen as the control group.The secretions from infection sites and blood specimens were collected from the patients with severe septic shock,the isolated pathogens were identified.The expression levels of TLRs signaling pathway-related factors TLR2 mRNA,TLR4 mRNA and nuclear factor-κB(NF-κB)in PBMCs and the levels of peripheral blood T lym-phocyte subsets and inflammatory factors were observed and compared between the study group and the control group,and between the death group and the survival group.RESULTS Totally 117 strains of pathogens were isola-ted from the101 patients with severe septic shock,68.38％of which were gram-negative bacteria.The expression levels of TLR2 mRNA,TLR4 mRNA and NF-κB in PBMCs and the levels of peripheral blood CD8+,interleukin-4(IL-4)and tumor necrosis factor-α(TNF-α)were significantly higher in the study group than in the control group(P＜0.05),while the levels of CD3+,CD4+,CD4+/CD8+,IL-10 and interferon-γ(IFN-γ)of the study group were significantly lower than those of the control group(P＜0.05).The expression levels of TLR2 mRNA,TLR4 mRNA and NF-κB in PBMCs and the levels of peripheral blood CD8+,IL-4 and TNF-α were significantly higher in the death group than in the survival group(P＜0.05);the levels of CD3+,CD4+,CD4+/CD8+,IL-10 and IFN-γ of the death group were significantly lower than those of the survival group(P＜0.05).CONCLUSION The gram-negative bacteria are dominant among the pathogens isolated from the patients with severe septic shock.The abnormal activation of TLRs signaling pathways,immunosuppression and aggravation of inflammatory reactions are closely associated with the severe septic shock and the prognosis.
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