Interleukin-3 and hematopoiesis.
Considerable information has accumulated over the past several years relating to the biological activities of IL-3 which supports that concept that IL-3 has a unique capacity to support the proliferation and differentiation of a wide spectrum of hematopoietic cells. The pleiotropic activity of IL-3 has in turn elicited considerable enthusiasm for clinical trials of IL-3 in humans. Such clinical trials are ongoing and will certainly reveal a variety of conditions that will benefit from IL-3 treatment alone or in combination with other lymphokines. Of particular note are conditions which would benefit from the proliferation and expansion of early myeloid progenitors. These include bone marrow reconstitutions, aplastic anemias, hematopoietic recovery following chemotherapy. A variety of data demonstrate that hematopoiesis is not dependent upon IL-3. Thus, alternative factors must exist that can also support the proliferation and differentiation of hematopoietic stem cells. This observation and the uniquely T cell origin of IL-3 have led to the concept the production of IL-3 has evolved within the immune system as a mechanism by which immunological reactions can broadly affect hematopoiesis. The lack of an essential role in constitutive hematopoiesis would be consistent with the divergence in the structure of the gene that is seen among species. Such a role would also predict that it will be easy to obtain mice in which the gene has been deleted by homologous recombination. Indeed, such mice will be essential to fully define the role that IL-3 has in the development and content of immune responses. Although IL-3 supports the proliferation of a variety of myeloid lineages and cells at various stages of differentiation, relatively little has been uncovered regarding the influence that IL-3 might have no differentiation. The results strongly suggest that IL-3 does not singularly control differentiation. The other extreme would suggest that IL-3 may support proliferation which allows the expression of a genetic program that is determined completely independent of IL-3. The most appealing hypothesis is that IL-3 can influence the outcome of a differentiation program. In particular, it can be hypothesized that a pluripotential stem cell that is proliferating in IL-3 has a somewhat different pattern of differentiation than cells proliferating in the presence of the factors that control constitutive hematopoiesis. Of particular interest are mechanisms by which IL-3 mediates its biological effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Ihle
J N
JN
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tenn.
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D016185:Receptors, Interleukin-3 / Q000502:physiology
D007377:Interleukin-3; D016185:Receptors, Interleukin-3; D004247:DNA