Efficacy of recombinant human macrophage colony-stimulating factor in combination with whole-body hyperthermia in the treatment of mice infected with the polycythemia-inducing strain of the Friend virus complex.
Macrophage colony-stimulating factor (M-CSF, CSF-1) and whole-body hyperthermia (WBH) were evaluated, alone or in combination, for their capability to influence disease progression in mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). DBA/2 mice were injected i.v. with FVC-P and were treated with 20 micrograms/dose M-CSF s.c. twice a day for 5 days beginning 6 days after injection of FVC-P and/or with WBH (between 38.8 degrees C and 40.2 degrees C) given on days 5 and 12 after FVC-P injection. Fourteen days after viral inoculation, mice were sacrificed and spleen cells evaluated for: 1) spleen focus-forming virus (SFFV), by the spleen focus-forming unit assay (SFFU); 2) SFFV mRNA and genomic DNA using, respectively, Northern and Southern analysis with a B-E-SFFV DNA probe; and 3) natural killer (NK) cell activity, by 51Cr-release assay. Treatment with M-CSF or WBH alone had a small effect on SFFU numbers but little or no effect on SFFV mRNA expression and SFFV-specific DNA. However, dramatically decreased levels of SFFU and SFFV mRNA and specific DNA fragments were observed in mice treated with M-CSF in combination with WBH, and NK cell activity was restored to normal. These results suggest the possibility that M-CSF may have a therapeutic effect in combination with WBH in the in vivo treatment of certain hematologic malignancies and/or retroviral infections.
Lu
L
L
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Shen
R N
RN
Zhou
S Z
SZ
Wu
B
B
Kim
Y J
YJ
Lin
Z H
ZH
Ruscetti
S
S
Ralph
P
P
Broxmeyer
H E
HE
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D003131:Combined Modality Therapy; D005260:Female; D005622:Friend murine leukemia virus / Q000235:genetics; D015870:Gene Expression; D006979:Hyperthermia, Induced; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007942:Leukemia, Experimental / Q000628:therapy*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D051379:Mice; D008811:Mice, Inbred DBA; D011086:Polycythemia / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D013154:Spleen / Q000473:pathology; D013155:Spleen Focus-Forming Viruses / Q000235:genetics; D014779:Virus Replication
D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma