Interleukin 3 perfusion prevents death due to acute anemia induced by monoclonal antierythrocyte autoantibody.
We have evaluated the therapeutic activity of rIL-3, in comparison with recombinant granulocyte-macrophage CSF (rGM-CSF) and recombinant erythropoietin (rEpo), on a lethal form of acute anemia induced by a single injection of a monoclonal IgG1 anti-mouse RBC (MRBC) autoantibody. Continuous perfusion of rIL-3 before the administration of anti-MRBC mAb prevented animals from the death due to anemia with a rapid recovery in greater than 90% of the cases, while only partial protection (one third of the cases) was obtained by rEpo perfusion, and no protection by rGM-CSF. Since the anti-MRBC mAb induced a marked agglutination of RBC in spleens and livers, and subsequent hemodynamic failure may be an additional contributing factor to the animals' death, the activation of Fc gamma receptor-dependent phagocytosis by rIL-3, as well as the increased number of monocytes/macrophages resulting from rIL-3 perfusion, may also facilitate rapid elimination of these agglutinated RBC, resulting in the further amelioration of the animals' survival. Our results suggest that the therapeutic effect of rIL-3 on anti-MRBC autoantibody-induced anemia is achieved by: (a) its activity to promote the growth and differentiation of erythroid progenitors responsive to Epo and of monocyte/macrophage lineage; and (b) its activity to enhance the phagocytic activity of macrophages to efficiently eliminate agglutinated RBC in spleens and livers.
Shibata
T
T
Department of Pathology, University of Geneva, Switzerland.
Kindler
V
V
Chicheportiche
Y
Y
Vassalli
P
P
Izui
S
S
D000208:Acute Disease; D000740:Anemia / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000276:immunology*; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004705:Endocytosis; D004912:Erythrocytes / Q000276:immunology*; D004921:Erythropoietin / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006400:Hematocrit; D007377:Interleukin-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010477:Perfusion; D011961:Receptors, Fc / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011961:Receptors, Fc; D011994:Recombinant Proteins; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor