Administration of recombinant interleukin-12 to mice suppresses hematopoiesis in the bone marrow but enhances hematopoiesis in the spleen

J Interferon Cytokine Res. 1995 Apr;15(4):377-83. doi: 10.1089/jir.1995.15.377.

Abstract

Although IL-12 has been reported to synergize with c-kit ligand (KL) in promoting hematopoietic stem cell proliferation in vitro, administration of recombinant mouse IL-12 (rIL-12) to normal mice caused a dose- and time-dependent anemia, leukopenia, and thrombocytopenia in vivo. Decreased numbers of bone marrow cells were recovered from the tibiae of IL-12-treated mice, and histologic examination of the marrow revealed a loss of mature neutrophils and red blood cell precursors. However, simultaneously with the suppression of hematopoiesis in the bone marrow, the IL-12-treated mice developed splenomegaly, which was largely caused by a marked enhancement of splenic extramedullary hematopoiesis of the erythroid, myeloid, and megakaryocytic lineages. These histologic observations were confirmed by colony-forming cell assays in which administration of IL-12 was shown to cause a time-dependent decrease in bone marrow CFU-GM, CFU-E, and BFU-E hematopoietic colony-forming cells while causing an increase in splenic CFU-GM and BFU-E colony-forming cells. All these effects were reversible upon cessation of IL-12 treatment. The observation that in IL-12-treated mice hematopoiesis was suppressed in the marrow but enhanced in the spleen suggests that myelosuppression was not caused by a direct effect of IL-12 on hematopoietic progenitors. It seems likely that myelosuppression was caused instead by an IL-12-induced alteration in the local environment of the marrow.

Publication types

  • Comparative Study

MeSH terms

  • Anemia / chemically induced
  • Animals
  • Bone Marrow / drug effects*
  • Dose-Response Relationship, Drug
  • Hematopoiesis / drug effects*
  • Hematopoiesis, Extramedullary / drug effects*
  • Interleukin-12 / pharmacology*
  • Leukopenia / chemically induced
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins / pharmacology
  • Reference Values
  • Spleen / drug effects*
  • Thrombocytopenia / chemically induced

Substances

  • Recombinant Proteins
  • Interleukin-12