Interleukin 6 receptor inhibitor tocilizumab suppresses cytokine expression, inflammasome activation and phagocytosis in a cell model of sepsis
Objective: Sepsis is a life-threatening condition, usually accompanied by excessive inflammation. Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin (IL) 6 receptor and has been studied in various inflammatory diseases, but little is known about its
effects in sepsis. This study aims to reveal the role of TCZ in inflammation during sepsis. Methods: Human monocyte cell line THP-1 was stimulated by lipopolysaccharide (LPS) as a cell model for sepsis. After TCZ treatment, the expression of cytokines tumor necrosis factor (TNF) and
IL10, the production of chemokine (C-C motif) ligand 2 (CCL2) and IL1B, and the expression of inflammasome factors NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1), were detected by qRT-PCR and ELISA. Phagocytosis assay was also performed to assess the phagocytosis activity
of TCZ-treated cells. Results: LPS stimulation significantly upregulated TNF and IL10 mRNA levels (P < 0.01) and CCL2 and IL1B production (P < 0.001), promoted NLRP3 and CASP1 levels (P < 0.01) and elevated phagocytosis activity
of THP-1 cells (P < 0.001). TCZ treatment had the opposite effects of decreasing TNF and IL10 mRNA levels (P < 0.05), CCL2 and IL1B production (P < 0.001), inhibiting NLRP3 and CASP1 (P < 0.01), and suppressing phagocytosis
activity (P < 0.001) compared to the LPS group. Conclusion: These results indicate the suppressive role of TCZ in cytokine production, inflammation activation and phagocytosis in sepsis cell model, implying its effects on controlling "cytokine storm" during sepsis. Thus TCZ
provides a promising strategy for treating sepsis.
Document Type: Research Article
Publication date: 01 November 2016
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