Identification of human immune cell subtypes most vulnerable to IL-1β-induced inflammatory signaling using mass cytometry

Cytokine storm is suspected of producing the overzealous immune response driving the severe cardiopulmonary complications that fuel high morbidity and mortality rates in certain COVID-19 infected individuals. IL-1β is one of the key inflammatory cytokines implicated in the cytokine storm syndrome. Inhibition of IL-1β induced cellular signaling with the IL-1 receptor antagonist anakinra has shown promise in treating cytokine storm and is proposed as a potential therapy for subjects with this severe complication of COVID-19. Yet little is known about the immune cell subtypes most responsive to IL-1β induced inflammatory signals in humans. We have developed a custom CyTOF panel and have identified the immune cell targets of IL-1β, and direct and indirect signaling, induced by IL-1β. Our data showing individual heterogeneity in response to IL-1β stimulation and inhibition by anakinra suggest that immune phenotyping of COVID-19 subjects using a similar approach could be effective in identifying those at risk for cytokine storm and those most likely to benefit from IL-1β inhibition.