Ns. Tare et al., ADMINISTRATION OF RECOMBINANT INTERLEUKIN-12 TO MICE SUPPRESSES HEMATOPOIESIS IN THE BONE-MARROW BUT ENHANCES HEMATOPOIESIS IN THE SPLEEN, Journal of interferon & cytokine research, 15(4), 1995, pp. 377-383
Although IL-12 has been reported to synergize with c-kit ligand (KL) i
n promoting hematopoietic stem cell proliferation in vitro, administra
tion 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 reveal
ed a loss of mature neutrophils and red blood cell precursors, However
, simultaneously with the suppression of hematopoiesis in the bone mar
row, 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 histolo
gic 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 c
ells while causing an increase in splenic CFU-GM and BFU-E colony-form
ing cells, All these effects were reversible upon cessation of IL-12 t
reatment, The observation that in IL-12-treated mice hematopoiesis was
suppressed in the marrow but enhanced in the spleen suggests that mye
losuppression was not caused by a direct effect of IL-12 on hematopoie
tic progenitors, It seems likely that myelosuppression was caused inst
ead by an IL-12-induced alteration in the local environment of the mar
row.