Comparison of the Antitumor Effect of Interferon and Interferon Inducers 1

Discussion and Summary

A comparison of the antitumor effect of IF and IF inducers (NDV, statolon, poly I·poly C, and poly A·poly U) was made in vitro and in vivo. In vitro three IF inducers (NDV, statolon, poly I·poly C) and IF were highly effective in inhibition of focus formation by MSV. In mice, NDV, statolon and poly I·poly C were equally effective as antitumor agents. IF and poly A·poly U at the dose level used were not effective. In hamsters, the antitumor effects of the inducers were much less pronounced than they were in mice.

The present findings suggest that in vivo the antitumor effects of IF inducers may bear a relationship to the amount of IF induced. In mice, poly A·poly U is a much poorer inducer of IF and a much weaker antitumor agent than poly I·poly C, NDV, or statolon. The lack of significant antitumor effect of passive IF in mice might be attributable to the dose used, which was even less than the amount of IF induced by poly A·poly U. Under other conditions IF can manifest antitumor activity (19-20).

Further correlation of IF and antitumor effects comes from the finding that poly I·poly C is a much poorer inducer of IF and a much weaker antitumor agent in hamsters than it is in mice. Although these correlations are consistent with the interpretation that IF is one of the mediators of the antitumor effects of IF inducers (4-7, 11), other mechanisms of their action are not excluded (12, 21). For example poly I·poly C could also exert an antitumor action by enhancing the cell-mediated immune response (21, 22) but comparative studies of enhancement of cell immunity are not available for NDV, poly A·poly U, or statolon. Another possible mechanism which is not dealt with in the present study is a direct chemotherapeutic effect of the inducers (22). This effect has been shown for poly I·poly C, but comparison with the other inducers has not been reported.

Correlation between two phenomena, such as IF levels and antitumor effects, does not establish a causal relationship between them. Indeed under other circumstances, there was an apparent lack of correlation between serum IF levels and antitumor action (23).