Endogenous production of TNF in mice with immune complex as a primer

C3H/He mice were immunized i.v. with sheep red blood cells (SRBC), and then the effect of i.v. challenge with SRBC on the priming of endogenous production of tumor necrosis factor (TNF) was investigated. Mice were immunized i.v. with 10(8) SRBC/mouse, and their serum TNF activity, triggered by 3 micrograms lipopolysaccharide (LPS) per mouse, was assayed by an in vitro cytotoxicity test using L-929 cells. Anti-SRBC antibodies were induced maximally in 2 weeks, but the acquired immunity did not affect TNF triggering. However, 9-10 weeks after the primary challenge, when there was still a relatively high antibody titer in the serum, i.v. rechallenge with 10(8) SRBC/mouse transiently enhanced the TNF activity triggered by LPS to about 10 times that in normal control mice. This priming effect of SRBC challenge was antigen specific, because challenge with horse red blood cells (HRBC) had no effect. SRBC opsonized with anti-treated with anti-SRBC antiserum or sonicated SRBC had no effect. These findings suggest two ways of facilitating the triggering of endogenous TNF production: booster challenge of immunized animals with the corresponding antigens makes them ready for TNF triggering, and direct injection of immune complexes, even into normal animals, makes them ready for triggering of TNF. The possible application of these findings for inducing endogenous TNF production in human cancer patients by use of immune complexes is discussed.