Tumor necrosis factor/cachectin is a less potent inducer of serum amyloid A synthesis than interleukin 1

Serum amyloid A (SAA) gene expression is known to be induced by interleukin (IL-1). The time course of in vivo induction of SAA synthesis by IL-1 was found to vary according to dose, in that SAA concentration was maximal at 6 hours following lower doses of IL-1, but greater at 20 hours when higher (greater than 500 ng) doses were administered. Because of recent reports that recombinant human tumor necrosis factor/cachectin (TNF) is a pyrogen similar to IL-1, its efficacy as an inducer of SAA synthesis was analyzed. TNF was found to be at least 100 fold less potent that IL-1 on a weight basis in both C3H/HeJ and C57BL/6 mice. However, C3H/HeJ mice were found to be more sensitive than C57BL/6 mice to both IL-1 and TNF stimulated SAA production. The magnitude of the acute phase SAA response was therefore found to be a function of the type of inflammatory mediator and genetic factors in the host.