Production of a Factor (CIF) from Normal Fibroblast Cells Inhibiting Tumor Necrosis Factor/Cachectin Production

Abstract

Murine embryonic fibroblast cells produce a factor designated cytotoxin-inhibiting factor (CIF) which inhibits tumor necrosis factor (TNF) and interleukin 1 production as well as tumoricidal activity by lipopolysaccharide-activated macrophages. This study determines the physiologic conditions of CIF production in serum-free medium. CIF production was largely dependent upon the presence of lipopolysaccharide. A quantitative correlation between fibroblast cell number, lipopolysaccharide concentration, and incubation time was established. Evidence is presented that CIF inhibited the production or release of TNF. CIF did not destroy TNF after production and release nor did it sequester secreted TNF. The supernatant fluids which inhibited TNF production did not suppress the capability of resting macrophages to phagocytize opsonized sheep erythrocytes, suggesting that only functions expressed in the activated state are inhibited.