Abstract
Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).
Keywords: COVID-19; IL-6; IL-6 neutralizing antibody; IL-6 receptor; hUCMSC; tocilizumab.
【저자키워드】 COVID-19, Tocilizumab, IL-6, IL-6 neutralizing antibody, IL-6 receptor, hUCMSC, 【초록키워드】 neutralizing antibody, Inflammation, ARDS, Severe COVID-19 pneumonia, therapy, Respiratory failure, Tocilizumab, interleukin-6, ELISA, Hyperinflammatory syndrome, Microarray, PBMC, Neutralizing, Responder, correlation, expression, Blood, acute respiratory distress, cellular, Concentration, PBMCs, Biological, IL-6 levels, proliferation, mononuclear cell, therapeutic potential, syndrome, inhibitory effect, IL-6R, treat, anti-inflammatory effect, supernatant, mRNA expression, cytokine secretion, peripheral, Cell, MTT, was measured, analyzed, was used, reported, evaluated, inhibited, functional, less, reached, Exogenous, IL-6 level, TCZ, umbilical, 【제목키워드】 ARDS, induction, Potential, TCZ,