HEMATOLOGIC EFFECTS OF RECOMBINANT HUMAN INTERLEUKIN-6 IN DOGS EXPOSED TO A TOTAL-BODY RADIATION-DOSE OF 2.4-GY

The hematologic effects of recombinant human interleukin-6 (rhIL-6) we re 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 mu g/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for the different hematologic parameters of the irradiated IL-B-treated dogs were compared with the data obtai ned from dogs who received TBI of 2.4 Gy and were treated with the car rier (control). No clear influence of IL-6 treatment on the pattern of recovery of lymphocytes could be detected in comparison to the irradi ated 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 thereaft er at approximately 30x10(3)/mu L. In three of the four IL-6-treated d ogs, however, thrombocyte counts increased at day 18 after the beginni ng of treatment. This increase occurred 7 days earlier than in the con trols. In two of the three dogs showing an accelerated recovery of pla telet counts, however, treatment with IL-6 caused a strong decrease in the erythrocyte counts associated with a prolonged depression in reti culocyte concentration. There was no influence on the recovery of bloo d granulocytes. In one of the animals responding with an accelerated t hrombocyte recovery, IL-6 had no adverse effect on erythropoiesis. How ever, IL-6 forced the recovery of blood granulocytes in the period bey ond day 10 after TBI. Another animal showed no influence of IL-6 on th rombocyte recovery but a strong depressive effect on erythrocyte and r eticulocyte 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 variation s between individuals, in contrast to what has been observed in irradi ated animals treated with granulocyte-macrophage or granulocyte colony -stimulating factor (GM- or G-CSF).