Autoregulatory Effect of Prostaglandin E2 on Interleukin 6 Production by Kupffer Cells

The Kupffer cell (KC) is the resident hepatic macrophage, whose functions include local intrahepatic immune responses implicated in tolerance induction, participation in the septic state, and regulation of hepatic regeneration. The ability of the KC to participate In these biologically diverse functions is thought to be due to its release of pleiotropic cytokines, such as interleukin 6 (IL-6), which can act locally in a paracrine fashion or as hormones at distant sites. Many of the KC′s secretory responses are carefully regulated in an autocoid fashion by the eicosanoid prostaglandin E₂ (PGE₂). The degree of regulation depends on the particular cytokine and local environmental factors. In this review, we describe our method for isolating KCs by their adherence to plastic and for testing their IL-6 and PGE₂ secretory responses to lipopolysaccharide. In comparing the responses of KCs from normal and regenerating rat livers, we describe an in vitro KC secretory pattern of eicosanoid inhibition of IL-6, whereas both responses to LPS are augmented in the KC during hepatic regeneration. Such an enhancement is consistent with the shared putative supportive roles of IL-6 and PGE₂ in liver regeneration.