Interleukin 1 receptor antagonist localization exclusively in non-parenchymal cells of the mouse liver.

The natural interleukin 1 receptor antagonist (IL-1ra) is induced in mouse liver after lipopolysaccharide (LPS) or recombinant interleukin 1 (IL-1) administration. Changes in hepatic IL-1ra mRNA concentration were measured following LPS injection to CBA mice. The results showed, that in vivo, IL-1ra transcripts were stimulated early at about 2h with maximal elevation at 4-6 h. Northern blot analysis of RNA extracted from primary cultures of mouse hepatocytes did not detect IL-1ra mRNA, although constitutive and stimulated contrapsin mRNA expression were easily demonstrated. Therefore, induction of IL-1ra mRNA in sinusoid lining cells of the mouse liver at 4 h after LPS injection was evidenced by in situ hybridization using the same specific cDNA probe as in the Northern blotting technique. Additionally, immunohistochemical studies revealed that IL-1 receptor antagonist protein was induced with LPS after 19 hours in sinusoid lining cells. The data deriving from Northern blotting, in situ hybridization and immunohistochemical studies, suggest that IL-1ra is formed exclusively in non-parenchymal liver cells.