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

J Exp Med. 1990 May 1;171(5):1809-14. doi: 10.1084/jem.171.5.1809.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Anemia / immunology
  • Anemia / pathology
  • Anemia / therapy*
  • Animals
  • Antibodies, Monoclonal*
  • Autoantibodies / immunology*
  • Colony-Stimulating Factors / therapeutic use*
  • Endocytosis
  • Erythrocytes / immunology*
  • Erythropoietin / therapeutic use*
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Growth Substances / therapeutic use*
  • Hematocrit
  • Interleukin-3 / administration & dosage
  • Interleukin-3 / therapeutic use*
  • Liver / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Perfusion
  • Receptors, Fc / physiology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Spleen / pathology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Colony-Stimulating Factors
  • Growth Substances
  • Interleukin-3
  • Receptors, Fc
  • Recombinant Proteins
  • Erythropoietin
  • Granulocyte-Macrophage Colony-Stimulating Factor