Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice

BackgroundThe role of Kupffer cell interleukin (IL)-1 in non-alcoholic steatohepatitis development remains unclear.AimsTo evaluate the role of Kupffer cell IL-1α, IL-1β or IL-1 receptor type-1 (IL-1R1) in steatohepatitis.MethodsC57BL/6 mice were irradiated and transplanted with bone marrow-derived cells from WT, IL-1α−/−, IL-1β−/− or IL-1R1−/− mice combined with Kupffer cell ablation with Gadolinium Chloride, and fed atherogenic diet. Plasma and liver triglycerides and cholesterol, serum alanine aminotransferase (ALT), liver histology and expression levels of inflammatory genes were assessed.ResultsThe ablation and replacement of Kupffer cells with bone marrow-derived cells was confirmed. The atherogenic diet elevated plasma and liver cholesterol, reduced plasma and liver triglycerides and increased serum ALT levels in all groups. Steatosis and steatohepatitis were induced, but without liver fibrosis. A reduction in the severity of portal inflammation was observed only in mice with Kupffer cell deficiency of IL-1α. Accordingly, liver mRNA levels of inflammatory genes encoding for IL-1α, IL-1β, TNFα, SAA1 and IL-6 were significantly lower in mice with Kupffer cell deficiency of IL-1α compared to WT mice.ConclusionSelective deficiency of IL-1α in Kupffer cells reduces liver inflammation and expression of inflammatory cytokines, which may implicate Kupffer cell-derived IL-1α in steatohepatitis development.