Interleukin-3: molecular biology and biologic activities

Abstract

IL-3 is one of the primary factors capable of supporting the growth and development of hematopoietic cells in culture. In comparison with the other hematopoietic growth factors, IL-3 preferentially supports the proliferation of early multilineage progenitors or progenitors at early stages of development within the different lineages. Subsequently, the developing cells lose responsiveness to IL-3 while acquiring dependence on the later acting factors: GM-CSF, G-CSF, M-CSF, or Ep. In addition, IL-3 has been demonstrated to exert biologic effects with other target cell populations. These activities include the potentiation of the IL-2-dependent growth of normal T cells; the potentiation of the IL-2-dependent secretion of IgG by activated B cells; and the potentiation of the activities of eosinophils, basophils, and monocytes. The importance of any of these activities of IL-3 in vivo in either normal or stressed animals remains to be determined. Initial experiments in primates with IL-3 have yielded results consistent with its role as a regulator of early hematopoietic cell development. Although administration of IL-3 alone has relatively little effect on the levels of circulating blood cells, this treatment primes the animals to become hyper-responsive to subsequent administration of the later acting factors GM-CSF and Ep. Thus combinations of factors, at least in some situations, can provide a more potent stimulation of hematopoiesis than provided by the individual molecules, a finding that should greatly expand the utility of the different hematopoietins to more indications in the clinic.