Kupffer cell autoregulation of IL-1 production by PGE 2 during hepatic regeneration

Abstract

The mammalian liver possesses the ability to regenerate to its original size after a 70% partial hepatectomy (PHx). The capacity of rat Kupffer cells (KC) isolated at specific intervals following PHx to produce interleukin-1 (IL-1) and prostaglandin E 2 (PGE 2) in response to endotoxin (LPS) was evaluated in standard RPMI-1640 (1200 μ M l-arginine) and arginine-depleted RPMI-1640 (10 μ M l-arginine) media. Regenerating liver KC 48–120 hr following PHx responded to LPS with a significantly greater ( p < 0.05) production of IL-1 in standard RPMI-1640. When 10 μ M l-arginine RPMI-1640 was used to simulate the high arginase activity low l-arginine levels of the hepatic microenvironment, regenerating liver KC production of IL-1 was further increased ( p < 0.05). During the same time period, regenerating liver KC also produced significantly ( p < 0.01) more PGE 2 than sham KC in both high and low arginine media. When the cyclooxygenase inhibitor indomethacin (10 μ M) was added to low arginine cultures, the PGE 2 production was inhibited, and IL-1 production was upregulated ( p < 0.05). We conclude that during hepatic regeneration KC IL-1 production is elevated but controlled in an autoregulatory fashion by KC PGE 2 production.