Interleukin-1, the “gate-keeper” of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. Expression, processing and secretion of IL-1 is tightly controlled, whilst dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates where a range and spectra of IL-1 secretion mechanisms have been described. We therefore use zebrafish embryos as an in vivo model for studying IL-1 mediated inflammation.

Structurally, zebrafish IL-1β shares a beta-sheet rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos.

Migration of macrophages and neutrophils was attenuated by caspase-1 and P2X7 inhibitors, which similarly inhibited the activation of NF-κB at the site of injury. Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo.

We are working on a range of mutants in this signalling pathway to genetically dissect Il-1 signalling in zebrafish.

See our review here.