A. Bernad et al., INTERLEUKIN-6 IS REQUIRED IN-VIVO FOR THE REGULATION OF STEM-CELLS AND COMMITTED PROGENITORS OF THE HEMATOPOIETIC SYSTEM, Immunity, 1(9), 1994, pp. 725-731
The development of blood cells from hematopoietic stem cells is contro
lled by multiple cytokines. These growth factors influence survival, c
ell cycle status, differentiation into lineage-committed progenitors,
final maturation into blood cells, and perhaps self-renewal of stem ce
lls. The specific contribution of IL-6 to these processes in vivo was
evaluated in mice with a targeted disruption of the IL-6 gene. Decreas
es in the absolute numbers of CFU-Sd12 and preCFU-S, as well as in the
functionality of LTRSC in these mutant mice, suggests a role for IL-6
in the survival, self-renewal, or both of hematopoietic stem cells an
d early progenitors. In addition, as a result of the IL-6 deficiency,
the control between proliferation and differentiation of the progenito
r cells of the granulocytic-monocytic, megakaryocytic, and erythroid l
ineages into mature blood cells is altered, leading to abnormal levels
of committed progenitors of these lineages and to a slow recovery fro
m hematopoietic ablation.