Effects of arsenicals on interferon formation and action.

Abstract

Interactions between arsenicals and interferon (IF) production and action are described. The protection afforded by poly I/poly C (PIC) against the death of mice from infection with the encephalomyocarditis virus (EMCV) was partially inhibited by sodium arsenite (NaAsO/sub 2/) and by roxarsone. Spleen of EMCV-exposed, NaAsO/sub 2/-treated mice contained 1 to 3 logs more virus than did spleen of saline solution-treated EMCV-exposed controls. A stimulating substance for the formation of plaques by the vesicular stomatitis virus (VSV) was present in spleen of the NaAsO/sub 2/-treated, EMCV-exposed mice. Detectable IF was not seen in spleen of NaAsO/sub 2/-treated, EMCV-exposed mice; low levels of IF were in spleen of EMCV-exposed control mice. Treatment of primary rabbit kidney (PRK) cell cultures with NaAsO/sub 2/ inhibited the induction of IF by PIC. In mouse embryo (ME) cells, NaAsO/sub 2/, sodium arsenate (Na/sub 2/HAsO/sub 4/), roxarsone, and p-arsanilic acid inhibited the action of mouse IF. The inhibition of IF action by the arsenicals was cell mediated and was time dependent, the inhibition by NaAsO/sub 2/ being ineffective before IF was added and 2 hours after IF was added, but being fully active at 0 and 1 hours after exposure of the cells to IF. Themore » NaAsO/sub 2/ did not alter IF activity directly. A dose-response relationship occurred between the concentration of arsenical tested and the percentage of inhibition of IF action which ensued. Data presented have indicated that high concentrations of arsenicals inhibited both the synthesis and the action of IF, whereas low concentrations of arsenicals increased the antiviral activity of low levels of IF. 11 references, 5 figures, 2 tables.« less