Biomaterial Database

Administration of dehydroepiandrosterone sulfate retards onset but not progression of autoimmune disease in NZB/W mice. 1997

S D Norton, and L L Harrison, and R Yowell, and B A Araneo

Pharmadigm, Inc., Salt Lake City, Utah 84109, USA.

NZB/W mice spontaneously develop an autoimmune disease characterized by the formation of anti-DNA antibodies and subsequent development of a fatal immune complex-mediated glomerulonephritis. Treatment of NZB/W F1 female mice with DHEAS, a precursor of DHEA, beginning at 2 months of age delayed the onset of autoimmune disease and prolonged survival. Animals treated with DHEAS beginning at 2 months of age had significantly lower anti-dsDNA serum antibody titers when compared to controls. Interestingly, DHEAS treatment had no effect on titers of anti-phosphatidylcholine (PtC) "natural" antibodies. Serum levels of IL-10, which increase with onset of disease, were also significantly reduced in mice treated with DHEAS beginning at 2 months of age. In contrast, if DHEAS treatment was started at 6 months of age, there was no effect on mortality rates. In addition, treatment of animals with DHEAS beginning at 6 months of age did not lower serum titers of anti-dsDNA and had no ameliorating effect on anti-PtC antibody production. Serum levels of IL-10 were also unaffected in mice treated with DHEAS beginning at 6 months of age. Together, these data suggest that parenteral administration of DHEAS is effective at delaying autoimmune disease and prolonging survival when given prior to the onset of symptoms. However, DHEAS treatment does not affect the course of disease when treatment begins after the onset of disease. We propose that DHEA(S) therapy used under similar conditions would not provide a clinically beneficial effect in the specific symptoms of immune complex-mediated glomerulonephritis.

UI	MeSH Term	Description	Entries
D007075	Immunoglobulin M	A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin.	Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D008814	Mice, Inbred NZB	An inbred strain of mouse that is widely used as a model for AUTOIMMUNE DISEASES such as SYSTEMIC LUPUS ERYTHEMATOSUS.	Mice, NZB,Mouse, Inbred NZB,Mouse, NZB,Inbred NZB Mice,Inbred NZB Mouse,NZB Mice,NZB Mice, Inbred,NZB Mouse,NZB Mouse, Inbred
D010713	Phosphatidylcholines	Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety.	Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D004797	Enzyme-Linked Immunosorbent Assay	An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.	ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005260	Female		Females
D005434	Flow Cytometry	Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.	Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D000367	Age Factors	Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.	Age Reporting,Age Factor,Factor, Age,Factors, Age
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000974	Antibodies, Antinuclear	Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.	Anti-DNA Antibodies,Antibodies, Anti-DNA,Antinuclear Antibodies,Antinuclear Autoantibodies,Antinuclear Autoantibody,Antinuclear Factors,Antinuclear Antibody,Antinuclear Factor,Anti DNA Antibodies,Antibody, Antinuclear,Autoantibody, Antinuclear,Factor, Antinuclear
D001323	Autoantibodies	Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.	Autoantibody