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Immune up-regulation and tumor apoptosis by androstene steroids
1Department of Microbiology, Immunology and Pathology, Medical College of Virginia, Virginia Commonwealth University, 1101 East Marshal Street, Richmond, VA 23298-0768, USA. loria@hsc.vcu.edu
Abstract:
beta Androstenes steroid up-regulates immunity to increase resistance against lethal infection and lethal radiation, and mediates a rapid recovery of hematopoietic precursor cells after radiation injury. beta Androstenetriol increases the levels of the TH(1) cytokines, IL-2, IL-3, IFN gamma and counteracts hydrocortisone mediated immune suppression. In contrast, 17 alpha androstenediol inhibits proliferation and mediates apoptosis in tumor cells of murine and human origin. Its epimer 17beta androstenediol does not. The antiproliferative functions of 17 alpha androstenediol are not dependent on either the estrogen or androgen receptors. Our findings show that beta androstenes and analogs protect the host from lethal infection by DNA or RNA viruses such as, herpesvirus type 2, coxsackievirus B4, influenza, and arthropod borne viruses. These androstenes also protected the host from lethal bacterial infections by Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumonia and from parasites infections, i.e. Cryptosporidium parvum, and malaria. In vivo, the level of potency follows the order: dehydroepiandrosterone<<