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Interleukin 3 perfusion prevents death due to acute anemia induced by monoclonal antierythrocyte autoantibody

Shibata, T.
Kindler, V.
Published in Journal of Experimental Medicine. 1990, vol. 171, no. 5, p. 1809-1814
Abstract 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.
Keywords Acute DiseaseAnemia/immunology/pathology/ therapyAnimalsAntibodies, MonoclonalAutoantibodies/ immunologyColony-Stimulating Factors/ therapeutic useEndocytosisErythrocytes/ immunologyErythropoietin/ therapeutic useGranulocyte-Macrophage Colony-Stimulating FactorGrowth Substances/ therapeutic useHematocritInterleukin-3/administration & dosage/ therapeutic useLiver/pathologyMiceMice, Inbred BALB CMice, Inbred StrainsPerfusionReceptors, Fc/physiologyRecombinant Proteins/administration & dosage/therapeutic useSpleen/pathology
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PMID: 2185334
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