Oromucosal interferon therapy: Pharmacokinetics and pharmacodynamics

Oromucosal administration of [I-125]-labeled recombinant human interferon-a lpha 1-8 (IFN-alpha 1-8), which is biologically active in the mouse, result ed in readily detectable levels of radioactivity in the serum of animals wi thin 5 min, Biologically active IFN could not be detected in the serum at a ny time after oromucosal administration, however, and SDS-PAGE analysis sho wed that the material present in the serum was of low molecular weight and most probably reflected absorption of degradation products following digest ion of IFN in the stomach and small intestine. Furthermore, oromucosal admi nistration of murine IFN-alpha/beta (MuIFN-alpha/beta) had no significant e ffect on the expression of IFN-responsive genes in either peripheral blood mononuclear cells or splenic lymphocytes even though in the same animals IF N treatment activated gene transcription locally in the lymphoid tissue of the oropharyngeal cavity and caused a marked systemic antiviral activity. O romucosal administration of MuIFN-alpha/beta had no significant effect on e ither the number of circulating peripheral blood leukocytes or the number o f granulocyte-macrophage colonies recovered from the bone marrow of IFN-tre ated animals, These results suggest that the mechanism of action of oromuco sal IFN therapy is distinct from that of parenterally administered IFN and mag involve, in the abundant lymphoid or epithelial tissue of the oropharyn geal cavity, either production of a soluble factor or activation of a speci fic cell population that enters the circulation to mediate the elimination of virus-infected or neoplastic cells.