Interleukin 6 receptor inhibitor tocilizumab suppresses cytokine expression, inflammasome activation and phagocytosis in a cell model of sepsis
- PMID: 29441967
- DOI: 10.1691/ph.2016.6713
Interleukin 6 receptor inhibitor tocilizumab suppresses cytokine expression, inflammasome activation and phagocytosis in a cell model of sepsis
Abstract
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.
Similar articles
-
Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages.Mol Immunol. 2013 Dec;56(4):471-9. doi: 10.1016/j.molimm.2013.05.005. Epub 2013 Aug 1. Mol Immunol. 2013. PMID: 23911403
-
The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome.J Ethnopharmacol. 2014 Aug 8;155(1):154-64. doi: 10.1016/j.jep.2014.04.053. Epub 2014 May 20. J Ethnopharmacol. 2014. PMID: 24858059
-
The anti-inflammatory effects of baicalin through suppression of NLRP3 inflammasome pathway in LPS-challenged piglet mononuclear phagocytes.Innate Immun. 2016 Apr;22(3):196-204. doi: 10.1177/1753425916631032. Epub 2016 Feb 9. Innate Immun. 2016. PMID: 26865578
-
Regulation and Function of the Nucleotide Binding Domain Leucine-Rich Repeat-Containing Receptor, Pyrin Domain-Containing-3 Inflammasome in Lung Disease.Am J Respir Cell Mol Biol. 2016 Feb;54(2):151-60. doi: 10.1165/rcmb.2015-0231TR. Am J Respir Cell Mol Biol. 2016. PMID: 26418144 Free PMC article. Review.
-
Tocilizumab in the treatment of myocardial infarction.Mod Rheumatol. 2018 Sep;28(5):733-735. doi: 10.1080/14397595.2018.1427457. Epub 2018 Jan 30. Mod Rheumatol. 2018. PMID: 29334841 Review.
Cited by
-
How COVID-19 induces cytokine storm with high mortality.Inflamm Regen. 2020 Oct 1;40:37. doi: 10.1186/s41232-020-00146-3. eCollection 2020. Inflamm Regen. 2020. PMID: 33014208 Free PMC article. Review.
-
COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.J Microbiol Immunol Infect. 2023 Jun;56(3):442-454. doi: 10.1016/j.jmii.2022.12.004. Epub 2022 Dec 15. J Microbiol Immunol Infect. 2023. PMID: 36586744 Free PMC article. Review.
-
An exploratory analysis of associations of genetic variation with the efficacy of tocilizumab in severe COVID-19 patients. A pharmacogenetic study based on next-generation sequencing.Front Pharmacol. 2024 Sep 13;15:1426826. doi: 10.3389/fphar.2024.1426826. eCollection 2024. Front Pharmacol. 2024. PMID: 39346556 Free PMC article.
-
Macrophage activation syndrome in Sepsis: from pathogenesis to clinical management.Inflamm Res. 2024 Dec;73(12):2179-2197. doi: 10.1007/s00011-024-01957-7. Epub 2024 Oct 15. Inflamm Res. 2024. PMID: 39404874 Review.
-
Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?J Autoimmun. 2020 Jul;111:102452. doi: 10.1016/j.jaut.2020.102452. Epub 2020 Apr 10. J Autoimmun. 2020. PMID: 32291137 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials