An epidermal cell-derived cytokine triggers the in vivo synthesis of serum amyloid A by hepatocytes.

Lipopolysaccharide (LPS) stimulates macrophages to produce a number of closely related soluble mediators, including interleukin 1 (IL 1), endogenous pyrogen (EP), and serum amyloid A (SAA) inducer, which are able to induce hepatocyte production of SAA, an acute-phase reactant. Keratinocytes also produce a soluble mediator, epidermal cell-derived thymocyte-activating factor (ETAF), which is very similar to IL 1. The experiments reported here show that unpurified ETAF-containing preparations, as well as ETAF after chromatography by gel filtration (Sephacryl S-200), anion-exchange on DEAE, phenyl-Sepharose, or isoelectrofocusing, were all able to induce the in vivo production of SAA by hepatocytes. Additionally, ETAF and SAA inducer exhibited the same pattern of temperature sensitivity. These observations add further support to the hypothesis that ETAF, IL 1, EP, and SAA inducer comprise a group of closely related mediators and that nonlymphoid cells can produce mediators that can regulate systemic inflammatory reactions.