Purified recombinant murine macrophage inflammatory protein-1α (rmuMIP-1α), a cytokine with myelopoietic activity in vitro, was assessed in vivo by injection into C3H/HeJ mice for effects on proliferation (percentage of cells in S phase DNA synthesis of the cell cycle) and absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the femur and spleen, and on nucleated cellularity in the bone marrow, spleen, and blood. rmuMIP-1α rapidly decreased cycling rates (at 2 to 10 μg/mouse i.v.) and absolute numbers (at 5 to 10 μg/mouse i.v.) of myeloid progenitor cells in the marrow and spleen. These effects were dose-and time-dependent and reversible. Suppressive effects were noted within 3 to 24 h for cell cycling and absolute numbers of progenitor cells in the marrow and spleen, and by 48 h for circulating neutrophils. A study comparing the effects of i.v. injection of rmuMIP-1α versus rmuMIP-1β, a biochemically similar molecule but with no myelosuppressive effects in vitro, demonstrated myelosuppression in vivo by rmuMIP-1α, but not by rmuMIP-1β. The results suggest that rmuMIP-1α has myelosuppressive activity in vivo and offers the possibility that it may be a useful adjunct to treatments involving cytotoxic drugs because of its reversible suppressive effects on normal progenitor cell cycling.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1992|
ASJC Scopus subject areas
- Immunology and Allergy