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Updated: Aug 4, 2026
Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Analysis of granulocyte-macrophage progenitor cells in patients treated with recombinant interferon alpha-2
Abstract:
The most common dose-limiting toxicity of alpha interferon has been leukopenia. It is well documented that interferon inhibits human multipotential, erythroid, and granulocyte-macrophage progenitor cells in vitro. Granulocyte-macrophage progenitor cells were evaluated by a colony-forming assay in patients treated with recombinant interferon alpha-2, and results of the assay were correlated with histologic findings in the same bone marrow aspirates and biopsy specimens from the same patients. Eleven patients received 10 million units/m2 interferon subcutaneously thrice weekly for three months. The bone marrow was evaluated on Day-3 (pretreatment) and Day 10 of treatment. Colony-forming granulocyte-macrophage cell count fell from 40.9 +/- 7.6 colonies per 10(5) cells before treatment to 9.3 +/- 1.2 at Day 10 (mean +/- SE, p less than 0.001). It is concluded that the leukopenia induced by interferon is caused by inhibition of maturation of marrow progenitor cells preventing the repopulation of the peripheral blood.
Insights
Recombinant interferon alpha-2 treatment significantly reduces granulocyte-macrophage progenitor cells in bone marrow. This inhibition of progenitor cell maturation leads to leukopenia, a common side effect of interferon therapy.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Leukopenia is a frequent dose-limiting toxicity associated with alpha interferon therapy.
- Interferon is known to inhibit human progenitor cells, including multipotential, erythroid, and granulocyte-macrophage types, in vitro.
Purpose of the Study:
- To evaluate the effect of recombinant interferon alpha-2 on granulocyte-macrophage progenitor cells in patients.
- To correlate in vitro colony-forming assays with bone marrow histology in patients receiving interferon therapy.
Main Methods:
- Eleven patients received subcutaneous recombinant interferon alpha-2 (10 million units/m2 thrice weekly for three months).
- Bone marrow evaluation included colony-forming assays and histologic examination of aspirates and biopsy specimens.
- Evaluations were performed pre-treatment (Day -3) and on Day 10 of treatment.
Main Results:
- A significant decrease in colony-forming granulocyte-macrophage cells was observed, falling from 40.9 +/- 7.6 colonies/10(5) cells pre-treatment to 9.3 +/- 1.2 colonies/10(5) cells at Day 10 (p < 0.001).
- Histologic findings were correlated with assay results.
Conclusions:
- Interferon-induced leukopenia is attributed to the inhibition of marrow progenitor cell maturation.
- This impaired maturation prevents the adequate repopulation of peripheral blood with white blood cells.
