Synergistic effect of human lactoferrin and recombinant murine interferon-gamma on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex.
Mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) have been used as a leukemic mouse model. In the present study, purified iron-saturated human lactoferrin (LF) and recombinant murine (rmu) interferon-gamma (IFN-gamma), alone or in combination, were used to influence disease progression in virally infected mice. DBA/2 mice were injected i.v. with FVC-P, and were treated s.c. with 100 micrograms LF at day 7, and/or rmuIFN-gamma at 5 x 10(4) units/day for 3 days beginning at day 6 after viral infection. Mice were assessed for survival, and also 14 days after virus inoculation, the mice were killed and spleen extracts were assessed for spleen focus forming virus (SFFV) titers by spleen focus forming unit (SFFU) assay, SFFV mRNA and genomic DNA expression, and natural killer (NK) cell activity. Treatment with LF or rmuIFN-gamma alone had little or no effect on SFFU numbers or SFFV mRNA or genomic DNA expression. However, dramatically decreased SFFV titers and levels of SFFV mRNA and genomic DNA were observed in mice treated with the combination of LF and rmuIFN-gamma. NK cell activity decreased by FVC-P was returned to normal levels by LF and rmuIFN-gamma. The combined treatment also enhanced the survival rates of FVC-P-infected mice. The results suggest synergistic suppressive effects of LF with rmuIFN-gamma on disease progression in FVC-P-infected mice. This information might be of significance as a potential therapy for patients with leukemia and those infected with retroviruses.
Lu
L
L
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202-5121.
Shen
R N
RN
Zhou
S Z
SZ
Srivastava
C
C
Harrington
M
M
Miyazawa
K
K
Wu
B
B
Lin
Z H
ZH
Ruscetti
S
S
Broxmeyer
H E
HE
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D005622:Friend murine leukemia virus; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D007781:Lactoferrin / Q000494:pharmacology / Q000627:therapeutic use*; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008811:Mice, Inbred DBA; D009929:Organ Size / Q000187:drug effects; D011086:Polycythemia / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D011994:Recombinant Proteins; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013154:Spleen / Q000473:pathology; D013155:Spleen Focus-Forming Viruses / Q000302:isolation & purification / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007781:Lactoferrin