Purified iron-saturated human lactoferrin (LF) was assessed in vivo for effects on the survival rates of C57BL × DBA/2 f1 (hereafter called BD2F1) (Fv-2ss) mice and titers of spleen focus-forming viruses (SFFV) in BD2F1 and DBA/2 (Fv-2ss) mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). LF prolonged the survival rates and decreased the titers of SFFV in mice given FVC-P. Titers of SFFV, assayed 14 days after administration of FVC-P, were measured by the spleen focus-forming unit assay in secondary mouse recipients. Decreases in titers of SFFV were apparent when LF was given in vivo as a single bolus dose of 200 µg within 2 h of the Friend virus complex (FVC), or as a total dosage of 200 µg given on days 1, 2, 4, 7, 9, and 11 after FVC-P, and to a lesser degree when LF was given as a total dosage of 200 µg on days 3, 4, 7, 9, and 11 after FVC-P. No decreases in titers of SFFV were detected when LF was given up to 3 days before or more than 3 days after FVC-P. LF did not appear to be directly inactivating the viruses as it did not inactivate the SFFV or the Friend murine leukemia helper virus in vitro. The results suggest that the protective effect of LF in vivo is probably due to an action on cells responding to the FVC or to an action on cells which influence the cells responding to the FVC or which influence the virus. It has been shown elsewhere that LF decreases the percentage of marrow and spleen hematopoietic progenitor cells that are in DNA synthesis in vivo and this may be the means by which the protective effect of LF is mediated in mice given the FVC.

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Supported by Public Health Service Grants CA 36464 and CA 36740 (to H. E. B.) from the National Cancer Institute and a grant from the Little Red Door, Marion County Cancer Society, Inc. (to L. L.). G. H. was a visiting investigator from the Veterinary School, Hannover, West Germany, and was supported in part by the Deutsche Forschungsgemeinschaft during some of these studies.

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