Abstract
OBJECTIVES: Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection. Due to lack of effective treatments, it has always been the difficulty and focus of clinical treatment of sepsis. Studies have shown that pro-brain-derived neurotrophic factor (proBDNF) binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor (p75(NTR)), which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis. This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75(NTR) in patients with sepsis and its effect on lymphocyte differentiation. METHODS: From the healthy donors (control group, n=40) and sepsis patients (sepsis group, n=40) admitted to the hospital for the first time, peripheral blood samples and blood routine clinical detection indicators were obtained. By using flow cytometry, the proportion of lymphocyte subsets and their expression of proBDNF/p75(NTR) were examined. The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide (LPS). Flow cytometry analysis technology was used to detect the expression of proBDNF/p75(NTR) on LPS-treated lymphocyte subsets. On this basis, we investigated the effects on lymphocyte differentiation by inhibiting p75(NTR). RESULTS: White blood cell count, neutrophil count, and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group; on the contrary, lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group (all P<0.001). The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group (both P<0.05). In the peripheral blood of sepsis patients, proBDNF expression was upregulated on CD19(+) B cells, whereas p75(NTR) expression was elevated on B cells, CD4(+) T cells, and CD8(+) T cells (all P<0.05). ProBDNF/p75(NTR) expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group (P<0.05), and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group. Inhibition of p75(NTR) increased CD4(+) T cell and CD19(+) B cell percentages, cytokine expression of IL-4 and IL-10, and reduced IL-1β and IL-6 production (all P<0.05). CONCLUSIONS: The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils. ProBDNF/p75(NTR) expression is upregulated in the peripheral blood lymphocytes of sepsis patients, and p75(NTR) inhibition may control lymphocyte differentiation involved in sepsis progression.