Hematologic effects of recombinant human interleukin-6 in dogs exposed to a total-body radiation dose of 2.4 Gy.

ABSTRACT

The hematologic effects of recombinant human interleukin-6 (rhIL-6) were studied in dogs exposed to a total-body irradiation (TBI) of 2.4 Gy. IL-6 was administered over a period of 14 days at a daily dose of 18 micrograms/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for the different hematologic parameters of the irradiated IL-6-treated dogs were compared with the data obtained from dogs who received TBI of 2.4 Gy and were treated with the carrier (control). No clear influence of IL-6 treatment on the pattern of recovery of lymphocytes could be detected in comparison to the irradiated control animals. The thrombocyte counts in the period from day 1 to 16 after TBI were similar for both groups of dogs, showing a sharp decrease in counts between days 6 and 12 with a stabilization thereafter at approximately 30 x 10(3)/microL. In three of the four IL-6-treated dogs, however, thrombocyte counts increased at day 18 after the beginning of treatment. This increase occurred 7 days earlier than in the controls. In two of the three dogs showing an accelerated recovery of platelet counts, however, treatment with IL-6 caused a strong decrease in the erythrocyte counts associated with a prolonged depression in reticulocyte concentration. There was no influence on the recovery of blood granulocytes. In one of the animals responding with an accelerated thrombocyte recovery, IL-6 had no adverse effect on erythropoiesis. However, IL-6 forced the recovery of blood granulocytes in the period beyond day 10 after TBI. Another animal showed no influence of IL-6 on thrombocyte recovery but a strong depressive effect on erythrocyte and reticulocyte counts. The results show that for standardized conditions of radiation-induced bone marrow damage, the pattern of response to IL-6 in different hematopoietic lineages may show considerable variations between individuals, in contrast to what has been observed in irradiated animals treated with granulocyte-macrophage or granulocyte colony-stimulating factor (GM- or G-CSF).