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

Exp Hematol. 1991 Sep;19(8):804-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Combined Modality Therapy
  • Female
  • Friend murine leukemia virus / genetics
  • Gene Expression
  • Hyperthermia, Induced*
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology
  • Leukemia, Experimental / therapy*
  • Macrophage Colony-Stimulating Factor / administration & dosage*
  • Mice
  • Mice, Inbred DBA
  • Polycythemia / therapy
  • RNA, Messenger / genetics
  • RNA, Viral / genetics
  • Recombinant Proteins
  • Spleen / pathology
  • Spleen Focus-Forming Viruses / genetics
  • Virus Replication

Substances

  • RNA, Messenger
  • RNA, Viral
  • Recombinant Proteins
  • Macrophage Colony-Stimulating Factor
  • Interferon-gamma