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[Interleukin-3: a preclinical study]
P Valent1, K Geissler, P Bettelheim
1I. Medizinische Universitätsklinik, Wien.
Recombinant hemopoietic cytokines play an increasing role in clinical hematology. The present preclinical study describes the biologic spectrum of a novel recombinant human cytokine, interleukin-3 (rhIL-3). In appropriate culture systems it could be demonstrated that interleukin-3 is a potent growth factor for hemopoietic stem cells. RhIL-3 induced, in addition, terminal differentiation of basophilic and eosinophilic granulocytes. Moreover, rhIL-3 was found to be an activation factor for mature blood basophils. Binding studies using radiolabelled rhIL-3 showed that the effects of interleukin-3 are mediated via specific cell surface membrane receptors. The in vivo effects of recombinant interleukin-3 were studied in a primate model (rhesus monkeys). In agreement with in vitro results interleukin-3 caused significant expansion of the functional stem cell pool. Moreover, interleukin-3 induced a marked increase in basophils and eosinophils. As side effects of recombinant interleukin-3 a slight to moderate elevation of plasma histamine levels was observed as well as the appearance of an erythematous exanthem. In summary, our studies provide evidence that IL-3 induces self renewal, growth and differentiation of human hemopoietic stem cells. Clinical indication areas for interleukin-3 obviously represent stem cell transplantation and the treatment of cytopenic disorders. Adverse side effects of this novel cytokine might arise from stimulation of growth and function of "allergic effector cells".
Recombinant hemopoietic cytokines play an increasing role in clinical hematology. The present preclinical study describes the biologic spectrum of a novel recombinant human cytokine, interleukin-3 (rhIL-3). In appropriate culture systems it could be demonstrated that interleukin-3 is a potent growth factor for hemopoietic stem cells. RhIL-3 induced, in addition, terminal differentiation of basophilic and eosinophilic granulocytes. Moreover, rhIL-3 was found to be an activation factor for mature blood basophils. Binding studies using radiolabelled rhIL-3 showed that the effects of interleukin-3 are mediated via specific cell surface membrane receptors. The in vivo effects of recombinant interleukin-3 were studied in a primate model (rhesus monkeys). In agreement with in vitro results interleukin-3 caused significant expansion of the functional stem cell pool. Moreover, interleukin-3 induced a marked increase in basophils and eosinophils. As side effects of recombinant interleukin-3 a slight to moderate elevation of plasma histamine levels was observed as well as the appearance of an erythematous exanthem. In summary, our studies provide evidence that IL-3 induces self renewal, growth and differentiation of human hemopoietic stem cells. Clinical indication areas for interleukin-3 obviously represent stem cell transplantation and the treatment of cytopenic disorders. Adverse side effects of this novel cytokine might arise from stimulation of growth and function of "allergic effector cells".