Affiliations: Virginia Commonwealth University Medical Center, Department of Microbiology and Immunology, Pathology and Emergency Medicine, VA, USA
Note: [] Correspondence to: Dr. Roger M. Loria, Professor of Microbiology, Immunology, Pathology and Emergency Medicine, Virginia Commonwealth University Medical Center, 1101 E. Marshall Street, Richmond, VA 23298-0678, USA. Tel.: +1 804 828 9717; Fax: +1 804 8285862; E-mail: [email protected]
Abstract: β Androstene steroids up-regulate immunity to increase host resistance against lethal infection by viruses, bacteria, and parasites. They also repair injury after lethal radiation exposure by mediating a rapid recovery of hematopoietic precursor cells. β Androstenes increase the levels of the TH1 cytokines, IL-2, IL-3, IFNγ and counteract hydrocortisone mediated immune suppression. Increased host resistance results in protection from lethal infection by DNA or RNA viruses such as herpes virus, coxsackievirus B4, influenza, and arthropod borne viruses. They provide similar protection against lethal Gram positive and negative bacteria as well as parasitic infections. During shock response, the hypothalamic-pituitary-adrenal axis (HPA) causes unchecked inflammation and sepsis. Androstenetriol treatment reduces Th2 and increases in Th1 cytokines, and significantly increases survival after severe trauma hemorrhage and shock by modulating the HPA response. In contrast to its epimer, 17α androstenediol inhibits proliferation and mediates apoptosis in tumor cells of murine and human origin and autophagy in human glioblastoma. The anti-proliferative functions or the immune up regulation by these neurosteroids are independent of either the estrogen or androgen receptors for activity. Results demonstrate that endoplasmic reticulum (ER) stress is linked to 17α androstenediol induced autophagy by PERK/eIF2 signaling in human malignant glioma cells and transformed fibroblast. The β androstene hormones increase host resistance to infections by enhancing cell mediated immunity while α androstene exerts an anti- tumor effect by apoptosis, autophagy and increase ER stress.
Keywords: Neurosteroids, immunity, infection, host resistance, programed cell death
