Development and application of an antibody that binds to interleukin-1β of various mammalian species for the treatment of inflammatory diseases

Abstract

Inflammation is provoked by host immune reactions to pathogenic or tissue injury and is arbitrated by cytokines. Among the pro-inflammatory cytokines, the tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) are main mediators of inflammation. The production of these pro-inflammatory cytokines is mainly triggered in macrophages by harmful stimuli including microbial pathogens, irritants, and toxic cellular components, and plays key roles in the palpation of the inflammatory response. Among the therapeutic antibodies for the treatment of inflammation, those targeting TNF-α (including adalimumab and infliximab) are frequently used in clinical settings. Although IL-1β is a key cytokine for the onset of inflammatory diseases, such as inflammatory bowel disease (IBD) and type 2 diabetes (T2DM), few therapeutic antibodies exist for this cytokine, with the exception of canakinumab. Canakinumab binds to human IL-1β, but does not bind to murine IL-1β, which hampers its experimental use. Therefore, inflammation-therapeutic antibodies that bind to IL-1β of various mammals are needed. In this study, we report the development of an antibody that bound to IL-1β of various mammalian species and exhibited therapeutic effects in inflammatory diseases.