New Cytokines with Thrombopoietic Activity

The use of growth factors to stimulate haemopoietic proliferation in various clinical conditions such as renal failure-associated anaemia, post-chemotherapy cytopenia and enhancement of bone marrow engraftment has been well described. Of the 3 haemopoietic lineages, the use of growth factors has been most beneficial in the erythroid and myeloid compartments. Currently, there are no cytokines available specifically for the purpose of stimulating thrombopoiesis. However, expanding knowledge of haemopoiesis in general and megakaryocytopoiesis in particular has led to an appreciation of the fact that multiple growth factors with overlapping or specific activities are involved in various stages of megakaryocyte proliferation and differentiation. Although application of early acting, multiline-age cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) has resulted in significant augmentation of thrombopoiesis in vitro, little such activity has been seen in vivo. The IL-3/GM-CSF fusion protein PIXY-321 (pixykine), also active in vitro, similarly has limited thrombopoietic effect in vivo. On the other hand, interleukin-6 (IL-6) and, in early studies, interleukin-11 (IL-11), which both augment IL-3-dependent progenitor proliferation and have significant megakaryocytopoietic activity in vitro, produce a more pronounced thrombopoietic effect. Further analyses and trials will be required to establish proper cytokine dosages, regimens and combinations in order to achieve maximal platelet enhancement.