Effects of rhIL-11 on normal dogs 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 irradiation (TBI) without marrow transplantation. Ten normal dogs were given rhIL-11 subcutaneously, twice daily for 14 days at varying doses, two dogs at 30 micrograms/kg/day, four dogs at 60 micrograms/kg/day, two dogs at 120 micrograms/kg/day, and two dogs at 240 micrograms/kg/day. Peripheral blood platelet counts increased in all dogs. The increase in platelet counts ranged from 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 platelet size was evident except at the dose of 240 micrograms/kg/day. There were no changes in the total white blood cell (WBC) count or differential. A higher proportion of megakaryocytes with a DNA content of 32N/64N was observed in dogs treated with rhIL-11 at day 7 (n = 6) than for control dogs that did not receive rhIL-11 (n = 7; p = 0.01). In both peripheral blood and marrow, significantly increased hematopoietic progenitors (i.e, colony-forming unit granulocyte/macrophage [CFU-GM]) were present 7 and 14 days after the start of treatment. Concentrations of serum fibrinogen 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 on day 15 after the start of rhIL-11 administration at a dose of 120 micrograms/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 micrograms/kg/day rhIL-11 subcutaneously in two divided doses for 28 days starting within 2 hours of TBI. The results in this group were compared with 10 dogs that had previously or concurrently been given 200 cGy without marrow grafting or hematopoietic 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 decreased 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 group. Treatment with rhIL-11 increased platelet counts, platelet size, ploidy number of megakaryocytes, and marrow and peripheral blood CFU-GM in normal dogs.(ABSTRACT TRUNCATED AT 400 WORDS)
Nash
R A
RA
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Seidel
K
K
Storb
R
R
Slichter
S
S
Schuening
F G
FG
Appelbaum
F R
FR
Becker
A B
AB
Bolles
L
L
Deeg
H J
HJ
Graham
T
T
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D004285:Dogs; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D017370:Interleukin-11 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D010976:Platelet Count / Q000187:drug effects / Q000528:radiation effects; D011003:Ploidies; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D017564:Radiation Pneumonitis / Q000517:prevention & control / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D007155:Immunologic Factors; D017370:Interleukin-11; D011994:Recombinant Proteins