Administration of recombinant human IL11 after supralethal radiation exposure promotes survival in mice: interactive effect with thrombopoietin.
In the present study, we evaluated the therapeutic potential of recombinant human IL11 in lethally irradiated C57BL6/J mice exposed to gamma rays. IL11 administered for 5 consecutive days beginning 2 h after total-body irradiation with 8 or 9 Gy 60Co gamma rays resulted in a significant increase in 30-day survival. When IL11 was administered, only a slight improvement in the hematopoietic status (both blood cell counts and progenitor cells) was observed after an 8-Gy exposure, and no improvement in hematopoietic reconstitution was observed after 9 Gy total-body irradiation. The enhancement of fibrinogen in the plasma of irradiated animals suggested the importance of infections in the death of animals. IL11 was able to limit the increase in fibrinogen levels. However, prevention of bacterial infections by antibiotic treatment, although it delayed death, was ineffective in promoting survival either in placebo-treated and IL11-treated mice. IL11 was administered along with thrombopoietin (TPO) or bone marrow transplantation to limit the hematopoietic syndrome, in addition to antibiotic treatment. When IL11 was combined with TPO, a potent stimulator of hematopoiesis, the survival of animals which had been irradiated with 10 Gy 137Cs gamma rays was increased significantly compared to those treated with IL11 or TPO alone. Furthermore, an interactive effect of TPO and IL11 on hematopoietic reconstitution was observed. Similarly, IL11 in combination with bone marrow transplantation enhanced survival after 15 Gy 137Cs gamma rays. These data suggest that the effect of IL11 on the hematopoietic system is only moderate when it is used alone in supralethally irradiated mice but that the effect is improved in the presence of a hematopoietic growth factor or bone marrow transplantation.
Van der Meeren
Anne
A
IPSN, DPHD, SARAM, B.P. no. 6, F-92265 Fontenay-aux-Roses cedex, France. anne.vandermeeren@ipsn.fr
Mouthon
Marc-André
MA
Gaugler
Marie-Hélène
MH
Vandamme
Marie
M
Gourmelon
Patrick
P
D000818:Animals; D001772:Blood Cell Count; D001773:Blood Cells / Q000187:drug effects* / Q000528:radiation effects; D001792:Blood Platelets / Q000187:drug effects / Q000528:radiation effects; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D004357:Drug Synergism; D005340:Fibrinogen / Q000378:metabolism; D005720:Gamma Rays / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects; D011994:Recombinant Proteins / Q000494:pharmacology; D015996:Survival Rate; D013926:Thrombopoietin / Q000494:pharmacology*; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects* / Q000401:mortality
D017370:Interleukin-11; D011994:Recombinant Proteins; D005340:Fibrinogen; D013926:Thrombopoietin