Oromucosal interferon therapy: Relationship between antiviral activity andviral load

Intraperitoneal (i.p.) administration of 20,000 IU recombinant murine IFN-a lpha (rMuIFN-alpha) was highly effective in protecting mice challenged i.p. with doses of encephalomyocarditis virus (EMCV) ranging from 44 to 440 LD5 0 (p < 0.001). Oromucosal (o.m.) IFN therapy was also found to be effective in protecting mice challenged with a lethal dose of EMCV. Thus, 40% of ani mals infected with 44 LD50 of EMCV and treated o.m. with 20,000 IU rMuIFN-a lpha survived infection with a mean survival time of 12.0 +/- 2.46 days rel ative to a mean of 6.11 +/- 0.38 days in the control group (p < 0.05). Orom ucosal IFN therapy was found to be ineffective, however, in animals infecte d with higher doses of EMCV (88-440 LD50), even though intraperitoneal admi nistration of the same dose of rMuIFN-alpha resulted in the survival of 90% , 50%, and 60% of animals infected with 88, 220, and 440 LD50 of EMCV, resp ectively. These results suggest that oromucosal IFN therapy is effective at relatively low viral load only and that the mechanism of action of oromuco sal IFN therapy may be different from that of parenterally administered IFN . Our results suggest that oromucosal IFN therapy may be most effective in chronic viral infections as an alternative to parenterally administered IFN , which is clinically effective but poorly tolerated.