In vivo stimulation of platelet production in a primate model using IL-1 and IL-3

The in vivo administration of various cytokines for hematopoietic stimulation has led primarily to the enhancement of the myeloid response with an insignificant contribution toward stimulating any increase in platelet production. Current studies have suggested that interleukin 1 (IL-1) and interleukin 3 (IL-3) are two of several factors that have an effect on either megakaryocyte formation or platelet production. The objective of our research was to investigate how the in vivo administration of IL-1 or IL-3 or a combination could be used to regulate megakaryocytopoiesis and platelet production in nonhuman primates. A single dose of IL-1 was able to stimulate an increase in platelet production for 3 weeks. The response was shown to be biphasic, with increased platelet counts of 46% and 49% above baseline on days 8 and 17, respectively. In contrast, the administration of IL-3 for 6 days led to an increase of 29% above baseline on day 17. An interesting observation was that the increased platelet counts were accompanied by a transient increase in the peripheral blood of a highly proliferative megakaryocyte colony-forming cell (MK-CFC), which attained a maximum concentration on day 7. The administration of a sequential combination of IL-1, then IL-3, was further evaluated to elucidate a possible potentiation on platelet production. The result was a similar increase in platelets to that observed in IL-1-only-treated monkeys for the first 7 days. However, the most significant effect was observed on day 17, when the 85% increase in platelets was demonstrated to be additive of the single-agent effects on that day. A reversal in the order of cytokine administration did not affect platelet production in this manner. In Il-1, then IL-3-treated monkeys, the increased platelet counts were also accompanied by an increase in the concentration of the peripheral blood MK-CFC from days 7 through 14. These results demonstrate that a combination of factors may be required to enhance platelet production, stimulating not only the formation of megakaryocytes but also stimulating the production and release of platelets into the peripheral blood.