Abstract
Patients who are severely affected by coronavirus disease 2019 (COVID-19) may develop a delayed onset ‘cytokine storm’, which includes an increase in interleukin-6 (IL-6). This may be followed by a pro-thrombotic state and increased D-dimers. It was anticipated that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID-19. However, clinical trials with TCZ have recorded an increase in D-dimer levels. In contrast to TCZ, colchicine reduced D-dimer levels in patients with COVID-19. To understand how the two anti-inflammatory agents have diverse effects on D-dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID-19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL-6, α-Defensin (α-Def), a pro-thrombotic peptide, and D-dimers. In contrast, treatment with colchicine reduced α-Def and Di-dimer levels. In vitro studies show that IL-6 stimulated the release of α-Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL-6; raising the possibility that the increase in IL-6 in patients with COVID-19 treated with TCZ triggers the release of α-Def, which promotes pro-thrombotic events reflected in an increase in D-dimer levels.
Keywords: inflammation; neutrophils; thrombosis.
【저자키워드】 Neutrophils, Inflammation, thrombosis., 【초록키워드】 COVID-19, coronavirus disease, Cytokine storm, clinical trial, Trial, thrombosis, Tocilizumab, IL-6, monoclonal antibody, interleukin-6, peptide, Coagulation, Patient, Colchicine, D-dimer level, Trigger, anti-inflammatory agent, D-dimer levels, positive, Administered, Effect, mitigate, event, polymerase chain, significantly increased, stimulated, performed, affected, develop, include, inhibit, reduced, treated, reflected, promote, increase in, recorded, human neutrophil, stimulatory, anti-IL-6 receptor, anticipated, patients with COVID-19, pro-thrombotic, raising, TCZ, treatment with colchicine, 【제목키워드】 Tocilizumab, Impact, Colchicine,