IL-6 trans-signaling inhibitor sgp130Fc suppresses inflammation and regulates immune cells in mice with sepsis

Abstract

Objective To investigate effects of IL-6 trans-signaling on immuno-inflammatory regulation in cecum ligation and puncture (CLP)-induced mice with sepsis. Methods Eighty mice were divided randomly into four groups: sham group (n=15), CLP group (n=30), CLP+sgp130Fc group (n=20) and sgp130Fc group (n=15). Sgp130Fc 0.5 mg/kg was injected intraperitoneally one hour after CLP in the CLP+sgp130Fc group and sgp130Fc group. Body weight and survival rate of mice were monitored daily during the research period (10 days). At 24 hrs after CLP, IL-6,IL-10, MCP-1 and TNFα were detected by ELISA; Peripheral blood leukocytes were separated and lymphocyte subgroups were sorted with the flow cytometry. Results Compared with sham group, the survival rate and body weight decreased significantly(P＜0.05). At 24 hrs after CLP, the expression of IL-6, IL-10, MCP-1 and TNFα increased significantly(P＜0.05). Lower level of the CD3+ CD4+ T cell and CD45+ CD19+ B cell but higher level of the CD3+ CD8+ T cell in the CLP group were found (P＜0.05). Compared with the CLP group, the survival rate was increased significantly(P＜0.05). At 24 hrs after CLP, the expression of IL-6, IL-10, MCP-1 and TNFα decreased significantly, and higher level of CD3+ CD4+ T cell and CD45+ CD19+ B cell but lower level of CD3+ CD8+ T cell in the CLP+ sgp130Fc group(P＜0.05) were recorded. Conclusions Inhibition of IL-6 trans-signaling can reduce mortality of mice with sepsis, which is potentially related to the regulation of early peripheral blood lymphocyte subgroups and inhibition of inflammatory responses.

Keywords

• sepsis|il-6 trans-signaling|cellular immunity|humoral immunity|inflammatory factor