Isolation of an inhibitor of type II interferon induction from tumor ascitic fluids.

A low-molecular-weight fraction (M.W. approximately 700) that specifically impairs the induction of type II interferon in mice by purified protein derivative of tuberculin or OK-432 was isolated from the cell-free ascitic fluid of mice bearing Ehrlich ascites carcinoma. Purification was achieved by ultrafiltration and gel filtration. The inhibitory activity of the isolated fraction was 10 times greater than that of the unfractionated starting material in the impairment of type II interferon induction. The significant inhibition was observed even when 0.2 ml of the 10,000-fold dilution of the fraction, which was previously adjusted to 0.25 A unit at 290 nm absorption, was once treated i.p. in normal mice 48 hr before challenge of type II interferon inducers. This fraction was stable to heating at 56 degrees for 60 min. The active component, however, did not affect the in vivo induction of type I interferon by polyriboinosinic-polyribocytidylic acid or tilorone-HCl. In parallel experiments, an identical low-molecular-weight fraction that impairs the type II interferon induction in mice was isolated from the ascitic fluids of rats bearing AH-100B ascites tumor and from a human hepatoma case with advanced cancer metastatic to the peritoneal cavity. However, nontumorous ascitic fluids obtained from adjuvant-stimulated mice and a human liver cirrhosis case did not contain any such inhibitory activity.