Stimulation of host defense against experimental cancer. II. Temporal and reversal studies of the zymosan effect.

I t has now been amply confirmed that the injection of zymosan can stimulate (6, s or depress (13, 27) host defenses against certain transplanted tumors, depending upon doses used and test circumstances. Initial experiments in our laboratory demonstrated that, if high chronic doses of zymosan were administered to mice, the animals frequently died with bacteremia of enteric origin. Indeed, these studied led to the discovery of Salmonellosis in the mouse colony (5). Based on this evidence of effect on host defense mechanisms, tests of low doses of zymosan were initiated to ascertain whether postulated defense stimulation (31) would occur which, in this case, would be active against tumors. For the past 3 years repeated experiments have been conducted in which the injection of 20 mg/kg zymosan intraperitoneally within several days of tumor implantation in 100+-day-old Swiss mice bearing Sarcoma 180 has caused 50 per cent or more regression of tumor in treated animals, as compared with 10 per cent or less regression among controls. Explorations into any possible role played by properdin in this phenomenon have been delayed by difficulties encountered in properdin assay procedures. In the meantime, information has been gathered regarding materials which can reverse zymosan activity, i.e., block the tumor regression phenomenon so that the tumors in treated animals grow and kill their hosts just like those in untreated controls. I t is the purpose of this paper to present the results of some of these studies on the reversal of the effect of zymosan on S-180 in Swiss mice and to explore further various theories which have been entertained with respect to zymosan-tumor interaction. Sarcoma 180 is recognized to be sensitive to regression; but it is this very property