Interleukin-1 accelertes murine granulocyte recovery following treatment with cyclophosphamide

This study investigated the effects of recombinant human interleukin-1 (rhIL-1α) on granulocyte recovery following treatment of mice with cyclophosphamide (CPM). CF₁ mice were injected with 0.5 μg rhIL-1α or heat-inactivated rhIL-1α 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 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.