loria

Phone: (804) 828-9717, (804) 828-5862
Dept. Fax: (804) 828-9946
e-mail: loria@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
P.O. Box 980678
1101 E. Marshall St., 7-068 Sanger Hall
Richmond, VA 23298-0678

The research is multi - disciplinary in nature. Its main theme centers on the pathogenic and immunological responses following virus infections, particularly human enteric viruses. Immune up Regulation after infections, cancer and following radiation are being studied.

Our laboratory has demonstrated an endocrine role in up-regulation of host resistance against lethal viral and bacterial infection as well as protection against radiation injury. Different hormones have been shown to induce apoptosis only in tumor cell line. Studies on the endocrine regulation of host immune resistance and apoptosis are ongoing. We have discovered a new group hormones - the androstenes which function to up-regulate host immunity, resulting in protection against lethal infections by viruses or bacteria. These effects appear to be achieved by up-regulation of the host resistance and not by direct destruction of the infectious organisms. These hormones, also counteract the immune suppressive effects of corticosteroids, and also may have a significant role in neuro-immune-regulation. Areas of possible application include counteracting stress-mediated immune suppression, and immunotherapy in infectious diseases and cancer.

Recently, we have completed a preclinical study demonstrating the ability of androstenetriol to counteract shock and maintain viability of an animal model following trauma and 50-60% blood loss.

Using animal model systems, it was shown that genetic predisposition to diabetes mellitus as characterized by the mutation diabetes in the mouse is associated with a greater susceptibility to infection with the human diabetogenic coxsackievirus B4. In Particular, the diabetic mutation on chromosome 4, mediates a more severe pancreatic pathology with destruction of beta cell, when the host is challenged with coxsackievirus B4. Moreover, genetic predisposition to diabetes without overt disease was shown to be associated with an impaired humoral immunity as evident from the inability of the host to produce neutralizing antibodies when challenged with this virus.

A dietary regime for the induction of Hypercholesteremia has been developed and studied extensively. Nutritionally induced hypercholesteremia was shown to mediate an immune suppression which was characterized by the inability of the host to reject tumors and an increased susceptibility to infections by coxsackievirus B and Listeria monocytogenes . The elevation in tissue-lipid deposition, was associated with an decrease in the cellular inflammatory response, and greater persistence of viral antigen. In this model, the increase in tissue lipid concentrations followed by an infection with a cardiotropic coxsackievirus B5, lead to the development of atherosclerosis which was absent when either virus or diet were administered separately. Recent studies have shown that dietary cholesterol also increase susceptibility to organophosphate pesticides such as diazinon. The common denominators between virus infection, dietary lipids and host immunity, in diabetes and atherosclerosis are illustrated by these findings.

The investigation of the pathophysiological changes following peroral infection by the human enteroviruses has been developed. The influences of viruses and bacterial infections on intestinal absorption, epithelial cell turnover rate and the local immunological responses have been studied.

Loria R.M., Host conditions affecting the course of coxsackievirus infections Eds. Friedman, H. and Bendinelli, M. in "Infectious Agents and pathogenesis: Coxsackieviruses a General Update." Plenum Press, Co. New York, N.Y. 1987.

Montgomery, L.B., Loria, R.M. and Chinchilli, V., Immunodeficiency as Primary Phenotype of Diabetes Mutation db: Studies with Coxsackievirus B4. Diabetes 39:675-683, 1990.

Loria R.M., and Padgett, D.A., Androstenediol Regulates systemic resistance to Against Lethal Infections in Mice. Archives of Virology 127:103-115, 1992.

Padgett, D.A. and Loria, R.M., In -Vitro Potentiation of Lymphocyte Activation by Dehydroepiandrosterone, Androstenediol, and Androstenetriol. J. Immunol.153:1544-1552, 1994.

Huynh PN, Loria RM. Contrasting effects of alpha- and beta-androstenediol on oncogenic myeloid cell lines in vitro. J Leukocyte Biol. 1997 Aug;62(2):258-6.

Ben-Nathan D. Padgett D.A., and Loria R.M., Androstenediol and Dehydroepiandrosterone Protect Mice Against Lethal Bacterial Infections and LPS Toxicity. Journal of Medical Microbiology 48:425-431, 1999.

Loria R.M., Conrad D.H., Huff H., and Ben-Nathan D., Adnrostenetriol and Androstenediol Protect Against Lethal Radiation and Restore Radiation Mediated Immune Injury. New York Academy of Sciences 917:860-868, 2000.

Loria R.M., Immune Up Regulation and Tumor apoptosis by Androstene steriods. Steroids 67:953-966, 2002.

Loria R.M. Effect of Dietary Hypercholesteremia on Host Immune Response. Yehuda S. and Mostofsky D.I. Eds. In Nutrients, Stress and Medical Disorders. Humana Press, Totowa NJ. 2006.

Andreea C. Marcu, R. , Nicole Kielar, Wayne Barbee, Hans Carter, Rao Ivatury, Kevin R. Ward, and Roger Loria. Effects of Androstrenetriol in a Rodent Model of Combined Hemorrhage and Tissue Injury. Resuscitation, 71: 379-386, 2006.

Andreea C. Marcu , Kristin E. Paccione , Robert F. Diegelmann , Rao R. Ivatury, Kevin R. Ward and Roger M. Loria . Androstenetriol Immunomodulation Improves Survival in a Sever Trauma-Hemorrhage Shock Model. The Journal of Trauma, Injury, Infection and Critical Care 63: (3) 662-669, Sept 2007.

Graf MR, Jia W, and Loria RM. The neuro-steriod, 3 androstene 17 diol exhibits potent cytotoxic effects on human malignant glioma and lymphoma cells through different programmed cell death pathways. British Journal of Cancer (2007), 1-9.