Interleukin-1 potentiates granulopoiesis and thrombopoiesis by producing hematopoietic factors in vivo.
In vivo administration of recombinant human interleukin-1 beta (rHu IL-1 beta) selectively enhanced the recovery from granulocytopenia and thrombocytopenia caused by whole body irradiation, in a dose dependent manner. Since IL-1 itself in vitro had no colony-stimulating activity (CSA), we studied whether IL-1 can produce hematopoietic factors in vivo, which in turn will promote granulopoiesis and thrombopoiesis. Serum from IL-1 injected mice showed marked granulocyte/macrophage CSA (GM-CSA), but little megakaryocyte CSA (Meg-CSA). Interestingly, strong megakaryocyte potentiator (Meg-POT) activity was detected in the serum. Further analysis of the serum by gel filtration chromatography showed that Meg-POT activity could be eluted in different fractions from GM-CSA. Since erythropoietin which is known to stimulate erythropoiesis also exhibited remarkable Meg-POT activity, serum from IL-1 injected mice were assayed for erythroid CSA. We found that unlike erythropoietin the serum showed no erythroid CSA. Taken together, these results suggest that IL-1 may potentiate granulopoiesis and thrombopoiesis by producing at least two distinct types of hematopoietic growth factors in vivo, namely granulocyte/macrophage colony-stimulating factor and a thrombopoietin-like factor.
Nakai
S
S
Cellular Technology Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Aihara
K
K
Hirai
Y
Y
D000380:Agranulocytosis / Q000628:therapy*; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D058851:GPI-Linked Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis; D006410:Hematopoiesis; D007375:Interleukin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D008533:Megakaryocytes; D008562:Membrane Glycoproteins; D000090204:Mesothelin; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000628:therapy*; D010976:Platelet Count; D011506:Proteins / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000628:therapy*; D013926:Thrombopoietin / Q000378:metabolism
D003115:Colony-Stimulating Factors; D058851:GPI-Linked Proteins; D006133:Growth Substances; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011506:Proteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin; D000090204:Mesothelin