Time Course of Interferon Levels,Antiviral State,2′,5′-Oligoadenylate Synthetase and Side Effects in Healthy Men

The kinetics of the biologic response following a single intramuscular injection of 18 × 10⁶ units of recombinant human interferon-α_2a (rHuIFN-α_2a) was investigated during 11 courses in 10 healthy individuals. Serial peripheral blood mononuclear cell (PBM) samples were assayed for their biologic responsiveness to rHuIFN-α_2a by measuring both their 2′,5′-oligoadenylate (2-5A) synthetase activity and their resistance to in vitro vesicular stomatitis virus (VSV) infection. A significant increase in 2-5A synthetase levels occurred at 6 h, and enzyme levels returned to baseline values between 96 and 104 h postinjection. Protection of PBMs from VSV infectivity began within 1 h and lasted up to 144 h postinjection. The clinical side effects induced by IFN administration and serum IFN levels were not parallel over time with the antiviral effects observed. This study defines the time course of the biologic response induced by rHuIFN-α_2a in healthy volunteers. A parallel time course between the induction of 2-5A synthetase activity and the development of the antiviral state in PBMs was demonstrated.