Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis: mechanism of reactive thrombocytosis

We studied the effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) on mouse megakaryocytopoiesis to evaluate the role of these cytokines in reactive thrombocytosis associated with inflammation. Injections of IL-1 or TNF to mice induced a significant increase in the megakaryocyte progenitor cell (CFU-Meg) count in the spleen. When IL-1 and TNF were injected simultaneously, the splenic CFU-Meg count was remarkably increased compared with mice injected with either IL-1 (p < 0.003) or TNF (p < 0.001) alone. On the other hand, neither IL-1 nor TNF showed any megakaryocyte-potentiating or -stimulating effects in vitro. In the sera obtained 4 h after administration of IL-1, TNF or both, high megakaryocyte potentiating activities were found. Furthermore, an extremely high level of IL-6 was detected in the serum after administration of both IL-1 and TNF. These results strongly suggest that IL-1 and TNF stimulate megakaryocytopoiesis indirectly via other cytokine(s) induced from accessory cells, and that increased levels of IL-1 and TNF play important roles in the development of reactive thrombocytosis caused by inflammation.