Combined effects of interleukin-3 and interleukin-11 on hematopoiesis in irradiated mice.
The survival rate and recovery of peripheral blood cells and platelets were studied in Balb/c mice subjected to different single doses of whole-body irradiation and treated with a combination of interleukin-3 (IL-3) and interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation, immediately followed by 2 and 5 days therapy of IL-3 and IL-11, respectively, increased the survival rate to 82% compared to 20% in untreated controls. In a second group of mice irradiated with 7 Gy, we observed significantly higher platelet, white blood cell (WBC), and red blood cell (RBC) counts after treatment with both cytokines, as compared to IL-3 or IL-11 alone or untreated controls. In addition, the survival rate of the mice with the combined therapy was also increased to 84%, compared to 48% in untreated controls. Irradiation (8.5 Gy) gave 100% mortality for the control mice, and therapy with combined IL-3 plus IL-11 had only a marginal effect. Interestingly, syngeneic bone marrow transplantation (BMT) alone, performed 16 hours after irradiation, increased the survival rate to 70%, while BMT combined with administration of IL-3 plus IL-11 increased it to 97%. Furthermore, BMT combined with cytokine administration could partially prevent the severe WBC and RBC depletion observed in mice treated with BMT alone and promoted a more rapid recovery of platelets and RBC. These data show that the combination of IL-3 and IL-11 has a radioprotective effect and can enhance recovery of platelets, WBC, and RBC in irradiated mice. Combined IL-3 plus IL-11 therapy may be clinically useful in myelodepression, especially in platelet depletion related to radiation therapy or chemotherapy, or after bone marrow transplantation.
Galmiche
M C
MC
Division of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Vogel
C A
CA
Delaloye
A B
AB
Schmidt
P M
PM
Healy
F
F
Mach
J P
JP
Buchegger
F
F
D000818:Animals; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D017370:Interleukin-11 / Q000008:administration & dosage*; D007377:Interleukin-3 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage; D014916:Whole-Body Irradiation
D004338:Drug Combinations; D017370:Interleukin-11; D007377:Interleukin-3; D011994:Recombinant Proteins