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L Stork, L Barczuk, M Kissinger and W Robinson
Department of Pediatrics, University of Colorado Health Sciences Center,
Denver.
This study investigated the effects of recombinant human interleukin-1
(rhIL-1 alpha) on granulocyte recovery following treatment of mice with
cyclophosphamide (CPM). CF1 mice were injected with 0.5 microgram rhIL- 1
alpha or heat-inactivated rhIL-1 alpha according to five different
regimens, before and/or following 200 mg/kg CPM. Significant neutrophilia
initially developed in treatment mice of all five regimens and accelerated
granulocyte recovery occurred in treatment mice of four IL-1 regimens.
Significant elevations in serum colony stimulating activity (CSA) occurred
in treatment mice at a number of time points studied. In addition, marked
increases in the percentage of maturing granulocyte precursors and in the
proportion of cells cycling in S and G2/M were observed in treatment marrow
throughout the IL-1 regimen. Before granulocyte recovery, premature nuclear
segmentation was noted in metamyelocytes of treatment marrow. Concomitant
with granulocyte recovery, treatment marrow was significantly more cellular
and contained more total CFU-GM, more CFU-GM in S phase, more cells in S
and G2/M, and more mitotic figures than control marrow. Splenic
myelopoiesis was also enhanced in treatment mice. These data suggest that
IL-1 significantly hastens granulocyte recovery following treatment with
CPM by enhancing both proliferation and maturation of myeloid precursors.
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