Abstract
Abstract
The accepted routes of interferon (IFN) administration in clinical applications are intramuscular, subcutaneous, intraperitoneal, intratumor, and intravenous. Recently, oral administration of interferons has been shown to cause a suppression of peripheral white blood cell (WBC) counts. Moreover, orally administered interferons mediate their peripheral WBC suppression via a different mechanism than that of intraperitoneally administered interferons. This study extends the previous studies to show that the peripheral WBC suppression induced by oral interferon treatment reflects an actual bone marrow suppression. The bone marrow-suppressive effects of orally and subcutaneously administered recombinant human IFN-αA/D (rHulFN-αA/D) have been partially characterized in kinetics studies and compared with the peripheral WBC-suppressive effects of orally and subcutaneously administered rHulFN-αA/D. Oral and subcutaneous administrations of rHulFN-αA/D cause a significant suppression of peripheral WBC counts with 1 day of rHulFN-αA/D administration. This suppression reaches its maximum level with 3 days of rHulFN-αA/D administration and plateaus over a 12-day treatment time. Similarly, oral and subcutaneous administrations of rHulFN-αA/D cause a significant suppression of bone marrow function with 1 day of rHulFN-αA/D administration. This suppression reaches its maximum level with 3 days of rHulFN-αA/D administration and plateaus over a 12-day treatment time. Thus, the WBC-suppressive and bone marrow-suppressive effects of rHulFN-αA/D administered either orally or subcutaneously parallel each other. The peripheral WBC-suppressive activities of orally and subcutaneously administered rHulFN-αA/D diminish at the same rate, after cessation of rHulFN-αA/D treatment. Peripheral WBC suppression is lost by 5 days after cessation of rHulFN-αA/D treatment. The mechanisms by which orally and subcutaneously administered interferons exert their bone marrow-suppressive effects differ, however. Bone marrow suppression mediated by subcutaneous administration of murine IFN-α/β (MulFN-α/β) is blocked by the presence of circulating antibodies to MulFN-α/β. In contrast, the bone marrow suppression mediated by oral administration of MulFN-α/β occurs even in the presence of circulating antibodies to MulFN-α/β. These results continue to support a potential clinical role for oral administration of interferons, particularly for the control of diseases of myelogenous origin.
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