title: Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (colony-forming units-granulocyte, macrophage) after acute administration of recombinant human IL-1 alpha.
abstract: Injection of human rIL-1 alpha in intact normal mice has positive and negative effects on myelopoiesis. Within 6 h postinjection, peripheral neutrophilia can be demonstrated. However, bone marrow and spleen cells capable of inhibiting CFU-granulocyte macrophage proliferation are detected between 6 and 48 h postinjection. These myelopoietic suppressor cells belong to the monocytic lineage and are identical to inhibitory cells induced by PGE2. Treatment of mice with indomethacin, a PG synthesis inhibitor, completely blocked the generation of IL-1-alpha-induced myelopoietic suppressor cells, and significantly enhanced femoral and splenic CFU-GM proliferation after a single injection of 0.4 microgram/mouse IL-1. The peripheral blood neutrophilia observed within 6 h after IL-1 injection was delayed to 18 to 24 h postinjection in indomethacin-pretreated mice. In mice treated with four consecutive daily injections of 0.4 microgram IL-1, a sustained peripheral neutrophilia was observed. IL-1 had little effect on femoral CFU-GM in these animals, however, splenic CFU-GM was increased 7- to 10-fold by 4 to 7 days postinjection. In IL-1 plus indomethacin-treated mice, sustained peripheral neutrophilia was observed although to a lesser degree than with IL-1 alone. Marrow CFU-GM were relatively unaffected, however, splenic CFU-GM were increased by 27-fold. These results indicate that the in vivo administration of IL-1 results in neutrophilia and generation of myelopoietic suppressive effects, mediated by cyclo-oxygenase pathway products. Blockade of PG synthesis by using the cyclo-oxygenase inhibitor indomethacin abrogates the myelopoietic suppressive effects associated with IL-1 administration and optimizes its myelopoietic stimulatory capacity. The inclusion of a cyclo-oxygenase inhibitor may have significant relevance to the clinical use of IL-1.
authors.affiliation: Laboratory of Hematopoietic Regulation, Sloan Kettering Institute, New York 10021.
authors.forename: L M
authors.initials: LM
authors.lastname: Pelus
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001853:Bone Marrow; D015232:Dinoprostone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006098:Granulocytes / Q000378:metabolism / Q000502:physiology; D006131:Growth Inhibitors / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology; D007213:Indomethacin / Q000008:administration & dosage; D007375:Interleukin-1 / Q000008:administration & dosage*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis* / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen
chemical_list: D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D015232:Dinoprostone; D007213:Indomethacin