EFFECTS OF RHIL-11 ON NORMAL CLOGS AND AFTER SUBLETHAL RADIATION

The effects of recombinant human interleukin-11 (rhIL-11) were studied in normal dogs and dogs given otherwise sublethal total-body irradiat ion (TBI) without marrow transplantation. Ten normal dogs were given r hIL-11 subcutaneously, twice daily for 14 days at varying doses, two d ogs at 30 mu g/kg/day, four dogs at 60 mu g/kg/day, two dogs at 120 mu g/kg/day, and two dogs at 240 mu g/kg/day. Peripheral blood platelet counts increased in all dogs. The increase in platelet counts ranged f rom 1.4 to 3.1 times the pre-treatment level. The greater increases of platelets were associated with higher doses (p=0.01). No change in pl atelet size was evident except at the dose of 240 mu g/kg/day. There w ere no changes in the total white blood cell (WBC) count or differenti al. A higher proportion of megakaryocytes with a DNA content of 32N/64 N was observed in dogs treated with rhIL-11 at day 7 (n=6) than for co ntrol dogs that did not receive rhIL-11 (n=7; p=0.01). In both periphe ral blood and marrow, significantly increased hematopoietic progenitor s colony-forming unit granulocyte/macrophage [CFU-GM]) were present 7 and 14 days after the start of treatment. Concentrations of serum fibr inogen increased by a median of 155 mg/dL at day 7 of rhIL-11 (p<0.01) . Cholesterol also increased by a median of 52 mg/dL at day 14 (p<0.01 ). There was a single death of a non-irradiated dog from pneumonitis o n day 15 after the start of rhIL-11 administration at a dose of 120 mu g/kg/day. All other non-irradiated dogs tolerated rhIL-11 without any significant adverse effects. Five dogs were given 200 cGy TBI without marrow grafting, followed by 240 mu g/kg/day rhIL-11 subcutaneously i n two divided doses for 28 days starting within 2 hours of TBI. The re sults in this group were compared with 10 dogs that had previously or concurrently been given 200 cGy without marrow grafting or hematopoiet ic growth factors. Two of the five treatment dogs died of pneumonitis on day 13 compared to one death among 10 control dogs on day 24. Among dogs that survived to hematologic recovery, the rhIL-11 dogs had decr eased platelet counts (<150,000) for a median of 24 days (range=24 to 41) compared to a median of 28 days (range=21-40) for the control grou p. Treatment with rhIL-11 increased platelet counts, platelet size, pl oidy number of megakaryocytes, and marrow and peripheral blood CFU-GM in normal dogs. There was a modest trend toward faster initial platele t recovery in the three surviving dogs after 200 cGy TBI. The pneumoni tis observed in three dogs treated with rhIL-11 may have had an infect ious etiology that was not evident on studies at necropsy, but further studies are warranted to determine whether rhIL-11 has any direct eff ects on the lung.