A novel cyprinid-specific IL-1 family cytokine activates inflammatory responses.

The interleukin-1 (IL-1) family is a central regulator of vertebrate inflammation. While eleven IL-1 family members have been identified in mammals, only three members, IL-1β, IL-18, and a teleost-specific novel IL-1 family member (nIL-1F), have been reported in fish to date. Here, we report a previously uncharacterized IL-1 family cytokine (termed nIL-1Fb) in cyprinid fish. The gene encoding nIL-1Fb is tandemly linked with the nIl-1f gene and is phylogenetically related to the nIl-1f, suggesting their common ancestral origin. We characterized the expression and function of nIL-1Fb in grass carp (Ctenopharyngodon idella), a major aquaculture species in Asia. Following infection with grass carp reovirus type II (GCRV-II), the nIl-1fb expression was markedly upregulated in the gills and hindgut. Immunofluorescence analyses revealed that nIL-1Fb was produced by virus infected cells and upregulated in infected tissues. Furthermore, nIL-1Fb co-localized with macrophage colony-stimulating factor receptor (MCSFR), indicating that monocytes/macrophages (Mo/Mφ) are the major source of nIL-1Fb. Functionally, nIL-1Fb not only induced the expression of pro-inflammatory genes (Tnf-α3, Il-8, and inos) but also enhanced the phagocytic activity of Mo/Mφ. However, nIL-1Fb exhibited a much weaker pro-inflammatory activity than IL-1β. Taken together, our findings identify nIL-1Fb as a cyprinid-specific pro-inflammatory cytokine, offering novel insights into the evolution and functional diversification of the IL-1 family in teleost fish.