The effects of systemic administrations of immune complex, complement activators, and insoluble particies on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by i.v. injection of OK-432, a streptococcal preparation, and measured by in vitro L-929 cytotoxicity assay. Intravenous injection of IgG-opsonized sheep red blood cells (108/mouse) enhanced OK-432-triggered TNF production significantly. This effect was maximal (about 30-fold enhancement) 1.5 to 3h after the injection and disappeared within 10h. Complement activators other than immune complex also possessed this activity. Zymosan (0.1 mg/mouse) enhanced OK-432-triggered TNF production maximally (about 25-fold) 3 to 6h after its i.v. injection, its effect lasting for 10h, and disappearing within 24h. Heat-aggregated IgG and cobra venom factor also had similar enhancing effects. In addition, systemic pretreatment with insoluble particles enhanced OK-432-triggered TNF production. The enhancement by latex beads (2 μl volume of solid/mouse) was maximal (about 60-fold) 3 to 6h after their i.v. injection, was sustained for at least 20h, and disappeared within 48h. Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects. Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.
*Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko-cho, Kanagawa, and †Research Development Corporation of Japan, Bunkyo-ku, Tokyo, Japan
Received October 29, 1986; accepted February 3, 1987.
Address correspondence and reprint requests to Dr. M. Satoh at Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko-cho, Kanagawa 199-01, Japan.
© Lippincott-Raven Publishers.