Peritoneal cells from C57B1/6 mice, incubated in vitro with a pure
mouse granuloma protein (MGP), decreased growth of Lewis
tumor cells (3LL). This
cytostatic activity was due to the release of stable
cytostatic factor(s) as determined by reduction of 125iododeoxyuridine (125I-UdR) incorporation in target cell cultures. Resident, inflammatory or bone-marrow-derived macrophages incubated with MGP had no
cytostatic effect on
tumor cells. Co-operation between lymphocytes and macrophages was required to express cytostasis when these cells were exposed to MGP. Maximal production of this factor by peritoneal cells was detected in the medium
after treatment with MGP for 6 hr.
Cytostatic activity was thermolabile (1 hr/56 degrees C). Fractionation of peritoneal cell supernatant by HPLC resulted in the recovery of one peak, eluting at 70 kDa, which was
cytostatic for 3LL cells. The
cytostatic supernatant was tested for
tumor necrosis factor activity (TNF): no correlation between TNF and
cytostatic activity was observed. Indeed, even high amounts of mouse rTNF did not affect 3LL cell growth. Moreover,
monoclonal antibodies (MAbs) to mouse TNF had no effect on cytostasis, indicating absence of synergistic interactions of the
cytostatic factor with low levels of mouse TNF.