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-1α

L. M. Pelus

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Injection of human rIL-1α 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-α-induced myelopoietic suppressor cells, and significantly enhanced femoral and splenic CFU-GM proliferation after a single injection of 0.4 μg/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 μg IL-1, a sustained peripheral neutrophilia was observed. IL-1 had little effect on femoral GFU-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.

Original languageEnglish (US)
Pages (from-to)4171-4179
Number of pages9
JournalJournal of Immunology
Volume143
Issue number12
StatePublished - 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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