title: Administration of recombinant interleukin-12 to mice suppresses hematopoiesis in the bone marrow but enhances hematopoiesis in the spleen.
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.
authors.affiliation: Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Tare
authors.forename: S
authors.initials: S
authors.lastname: Bowen
authors.forename: R R
authors.initials: RR
authors.lastname: Warrier
authors.forename: D M
authors.initials: DM
authors.lastname: Carvajal
authors.forename: W R
authors.initials: WR
authors.lastname: Benjamin
authors.forename: J H
authors.initials: JH
authors.lastname: Riley
authors.forename: T D
authors.initials: TD
authors.lastname: Anderson
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
mesh_terms: D000740:Anemia / Q000139:chemically induced; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects*; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects*; D018664:Interleukin-12 / Q000494:pharmacology*; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013154:Spleen / Q000187:drug effects*; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D011994:Recombinant Proteins; D018664:Interleukin-12