biostudies-literatureUnknown88(3)Doyle EB<h4>Aims</h4>To assess the potential of interleukin-6 (IL-6) signalling blockade in the lung to treat SARS-CoV-2 infection via model-based simulation by exploring soluble IL-6 receptor (sIL-6R) sequestration by tocilizumab (TCZ) and IL-6 sequestration by siltuximab (SIL).<h4>Methods</h4>Literature values of IL-6, IL-6 antagonist SIL, sIL-6R, IL-6R antagonist TCZ and their respective binding constants were used to develop a model to predict the impact of treatment on IL-6 signalling. Models were used to generate simulated bronchoalveolar lavage fluid concentrations for normal subjects, subjects at risk of developing acute respiratory distress syndrome (ARDS), and subjects with ARDS under 4 conditions: without treatment; treatment with TCZ; treatment with SIL; and treatment with TCZ + SIL.<hBritish journal of clinical pharmacology1043-1053https://www.ebi.ac.uk/biostudies/studies/S-EPMC8444890biostudies-literatureCOVID-19 acute respiratory distress syndrome: A simulation study of the effects of combination therapy with tocilizumab and siltuximab.PMC8444890Bentley DDoyle EBDodds MGfalseCOVID-19 acute respiratory distress syndrome: A simulation study of the effects of combination therapy with tocilizumab and siltuximab.<h4>Aims</h4>To assess the potential of interleukin-6 (IL-6) signalling blockade in the lung to treat SARS-CoV-2 infection via model-based simulation by exploring soluble IL-6 receptor (sIL-6R) sequestration by tocilizumab (TCZ) and IL-6 sequestration by siltuximab (SIL).<h4>Methods</h4>Literature values of IL-6, IL-6 antagonist SIL, sIL-6R, IL-6R antagonist TCZ and their respective binding constants were used to develop a model to predict the impact of treatment on IL-6 signalling. Models were used to generate simulated bronchoalveolar lavage fluid concentrations for normal subjects, subjects at risk of developing acute respiratory distress syndrome (ARDS), and subjects with ARDS under 4 conditions: without treatment; treatment with TCZ; treatment with SIL; and treatment with TCZ + SIL.<h2022-01-01T00:00:00Z2022 Mar2025-06-01T00:57:00.405Z2025-06-01T00:57:00.405ZS-EPMC84448903431851610.1111/bcp.15009