Treatment of mice with macrophage colony stimulating factor (CSF-1) prevents the in vivo myelosuppression induced by murine alpha, beta, and gamma interferons.
Interferon (IFN) treatment has been shown to suppress the bone marrow in mice and humans, causing a leukopenia. In vitro studies with the mouse system have shown that colony stimulating factors (CSFs) antagonize the bone marrow suppressive, but not the antiviral or antiproliferative activities of IFNs. Partially purified murine macrophage colony stimulating factor (CSF-1) was evaluated for its ability to antagonize the myelosuppressive effect of murine (Mu) IFNs in vivo. All three interferon types (MuIFN-alpha, MuIFN-beta, and MuIFN-gamma) were used. IFNs and CSF-1 were administered subcutaneously for 3 successive days, blood was drawn by retro-ocular bleeding, and myelo-suppression was quantitated by subjecting the blood to total white blood cell (WBC) counts and to differential counts. The IFNs had similar effects, though MuIFN-gamma was a significantly more potent (50- to 100-fold) myelosuppressive agent than MuIFN-alpha or MuIFN-beta. Treatment with each of the three IFNs caused a reduction in the total WBC count (up to 40% reduction) and a generalized reduction of each of the three major leukocytes (lymphocytes, segmented polymorphonuclear leukocytes, and monocytes). Treatment with CSF-1 did not affect the total WBC count, but did cause a shift in the relative ratios of the leukocytes, decreasing the relative percentage of lymphocytes, and increasing the relative percentage of segmented polymorphonuclear leukocytes and monocytes. Combined treatment with CSF-1 and IFN inhibited the myelosuppressive activity of the IFNs, and restored the total WBC count to control levels. This restoration was largely due to increased levels of segmented polymorphonuclear leukocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005260:Female; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D007958:Leukocyte Count; D007970:Leukopenia / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000502:physiology*
D003115:Colony-Stimulating Factors; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma