Methylxanthine treatment of rats reduces 2,5-oligoadenylate synthesis in liver nuclei

The in vivo effects of methylxanthines on 2',5'-oligoadenylate (2,5An) synthetase activity, an interferon-inducible enzyme, were investigated in rat liver nuclei. Caffeine given at 50 mg/kg ip or theobromine given at 80 mg/kg sc twice daily for 5 d resulted in a 60% reduction (p less than 0.01 and p less than 0.05, respectively) of 2,5An synthetase activity in liver nuclei. Theophylline given at 80 mg/kg sc by the same regimen reduced the enzyme activity by 42% (p less than 0.05). Nuclear 2'-phosphodiesterase activity, which catalyzes the degradation of 2,5An, remained low and unchanged following the drug treatments. When animals receiving caffeine were also given the interferon inducer poly(I)poly(C) at 500 micrograms/kg ip once daily for the last 2 d of caffeine treatment, it resulted in the same fourfold increase in 2,5An synthetase activity as shown with poly(I)poly(C) alone. These results suggest that methylxanthines may interact with interferon-mediated actions. The reason for the inhibitory effect of methylxanthines on the basal but not on the induced 2,5An synthetase remains to be investigated.