ABSTRACT
The regulatory influences on Kupffer cell, or macrophage, activation very likely also change significantly over time. Virtually all of the products of activated Kupffer cells, such as interleukin (IL)-1, tumor necrosis factor (TNF), IL-6, prostaglandin (PGE)2, etc., have regulatory or counterregulatory influences on all other Kupffer cell functions. Loss of Kupffer cell LPS responsiveness appears to be secondary to lipopolysaccharide (LPS)-stimulated production of PGE2. In macrophages, the production of IL-1 is inhibited by PGE2 and by IL-1 itself. At the same time, IL-1-a can induce production of IL-1-β, and IL-1-β is capable of inducing IL-1-a synthesis. Furthermore, it is clear that Kupffer cells or other macrophagelike cells do not function autonomously, but rather interact continuously with adjacent cells. Thus, the Kupffer cell activation state is also influenced by complex cytokine networks. Future discoveries will likely suggest new ways to intervene clinically to optimize the activation state of Kupffer cells and other macrophages so that patient mortality and morbidity are decreased.
