{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:20:00Z","timestamp":1791148800951,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T00:00:00Z","timestamp":1243468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>While estrogen treatment exacerbates disease in models of systemic lupus erythematosus (SLE), the effects of progesterone are unclear. This study was undertaken to assess the effects of continuous progesterone treatment on autoantibody production and spontaneous glomerulonephritis (GN) in a mouse model of SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female (NZB \u00d7 NZW)F<jats:sub>1<\/jats:sub> (NZB\/NZW) mice were treated with vehicle, 2 mg of depot medroxyprogesterone acetate (DMPA), or 10 mg of DMPA every 6 weeks. Survival, proteinuria, and serum anti\u2013double\u2010stranded DNA (anti\u2010dsDNA) levels were monitored. At 39 weeks of age, kidneys were analyzed for abnormalities and glomerular accumulation of IgG subclasses and C3. Spleen leukocyte subsets were also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DMPA treatment reduced mortality in a dose\u2010dependent manner in association with reduced proteinuria and glomerular damage. High\u2010dose DMPA treatment resulted in a reduction of total serum IgG and IgG2a anti\u2010dsDNA antibody levels, whereas IgG1 anti\u2010dsDNA antibody levels were modestly increased. High\u2010dose DMPA reduced glomerular accumulation of IgG1, IgG2a, IgG3, and complement, while low\u2010dose DMPA decreased glomerular IgG2a and IgG3 levels compared with vehicle treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that treatment of premorbid female NZB\/NZW mice with DMPA reduces mortality and attenuates spontaneous GN, likely through multiple mechanisms, including altered ratios of protective Th2\u2010related IgG antibodies versus nephritogenic Th1\u2010related IgG autoantibodies. Thus, estrogen and progesterone may have disparate effects on lupus autoimmunity, lending new significance to observed hormonal imbalances in patients with SLE. These data also suggest that treatment of SLE patients with DMPA may have therapeutic benefit.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24548","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T11:35:01Z","timestamp":1243510501000},"page":"1775-1784","source":"Crossref","is-referenced-by-count":55,"title":["Decrease in glomerulonephritis and Th1\u2010associated autoantibody production after progesterone treatment in NZB\/NZW mice"],"prefix":"10.1002","volume":"60","author":[{"given":"Grant C.","family":"Hughes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly 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