Oromucosal Interferon Therapy: Pharmacokinetics and Pharmacodynamics
| Autor: | Chantal Maury, Dominique Weill, Jean François Meritet, Michael G. Tovey, Ahmed Lasfar, Pierre Eid |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Immunology
Population Administration Oral Biology Peripheral blood mononuclear cell Mice Pharmacokinetics Interferon Virology 2' 5'-Oligoadenylate Synthetase medicine Animals Antigens Ly Humans Tissue Distribution Lymphocytes education education.field_of_study Hematologic Tests Histocompatibility Antigens Class I Mouth Mucosa Cell Biology Recombinant Proteins Small intestine medicine.anatomical_structure Lymphatic system Mechanism of action Interferon Type I Leukocytes Mononuclear Electrophoresis Polyacrylamide Gel Female Bone marrow medicine.symptom Spleen medicine.drug |
| Zdroj: | Journal of Interferon & Cytokine Research. 19:157-169 |
| ISSN: | 1557-7465 1079-9907 |
| Popis: | Oromucosal administration of [125I]-labeled recombinant human interferon-alpha1-8 (IFN-alpha1-8), which is biologically active in the mouse, resulted in readily detectable levels of radioactivity in the serum of animals within 5 min. Biologically active IFN could not be detected in the serum at any time after oromucosal administration, however, and SDS-PAGE analysis showed that the material present in the serum was of low molecular weight and most probably reflected absorption of degradation products following digestion of IFN in the stomach and small intestine. Furthermore, oromucosal administration of murine IFN-alpha/beta (MuIFN-alpha/beta) had no significant effect on the expression of IFN-responsive genes in either peripheral blood mononuclear cells or splenic lymphocytes even though in the same animals IFN treatment activated gene transcription locally in the lymphoid tissue of the oropharyngeal cavity and caused a marked systemic antiviral activity. Oromucosal administration of MuIFN-alpha/beta had no significant effect on either the number of circulating peripheral blood leukocytes or the number of granulocyte-macrophage colonies recovered from the bone marrow of IFN-treated animals. These results suggest that the mechanism of action of oromucosal IFN therapy is distinct from that of parenterally administered IFN and may involve, in the abundant lymphoid or epithelial tissue of the oropharyngeal cavity, either production of a soluble factor or activation of a specific cell population that enters the circulation to mediate the elimination of virus-infected or neoplastic cells. |
| Databáze: | OpenAIRE |
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