Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice

The ionizing radiation-induced hemopoietic syndrome is characterized by def ects in immune function and increased mortality due to infections and hemor rhage. Since the steroid 5-androstene-3 beta,17 beta-diol (5-androstenediol , AED) modulates cytokine expression and increases resistance to bacterial and viral infections in rodents, we tested its ability to promote survival after whole-body ionizing radiation in mice. In unirradiated female B6D2F1 mice, sc AED elevated numbers of circulating neutrophils and platelets and induced proliferation of neutrophil progenitors in bone marrow. In mice exp osed to whole-body Co-60 gamma-radiation (3; Gy), AED injected 1 h later am eliorated radiation-induced decreases in circulating neutrophils and platel ets and marrow granulocyte-macrophage colony-forming cells, but had no effe ct on total numbers of circulating lymphocytes or erythrocytes. In mice irr adiated (0, 1 or 3 Gy) and inoculated four days later with Klebsiella pneum oniae, AED injected 2 h after irradiation enhanced 30-d survival. Injecting AED 24 h before irradiation or 2 h after irradiation increased survival to approximately the same extent. In K. pneumoniae-inoculated mice (irradiate d at 3-7 Gy) and uninoculated mice (irradiated at 8-12 Gy), AED (160 mg/kg) injected 24 h before irradiation significantly promoted survival with dose reduction factors (DRFs) of 1.18 and 1.26, respectively. 5-Androstene-3 be ta-ol-17-one (dehydroepiandrosterone, DHEA) was markedly less efficacious t han AED in augmenting survival, indicating specificity. These results demon strate for the first time that a DHEA-related steroid stimulates myelopoies is, and ameliorates neutropenia and thrombocytopenia and enhances resistanc e to infection after exposure of animals to ionizing radiation. (C) 2000 In ternational Society for Immunopharmacology. Published by Elsevier Science L td. All rights reserved.