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.
Dan
K
K
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Gomi
S
S
Inokuchi
K
K
Ogata
K
K
Yamada
T
T
Ohki
I
I
Hasegawa
S
S
Nomura
T
T
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003114:Colony-Forming Units Assay; D005260:Female; D005269:Femur; D006410:Hematopoiesis / Q000187:drug effects*; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology* / Q000633:toxicity; D008533:Megakaryocytes / Q000187:drug effects*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013922:Thrombocytosis / Q000139:chemically induced / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000633:toxicity
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha