title: Comparative influence of steroid hormones and immunosuppressive agents on autoimmune expression in lacrimal glands of a female mouse model of Sjögren's syndrome.
abstract: OBJECTIVE
  Previous research has demonstrated that testosterone therapy causes a profound suppression of autoimmune disease in lacrimal glands of female mouse models of Sjögren's syndrome. The aim of the present study was to determine whether other anabolic androgens, nonandrogenic steroids, or immunosuppressive agents might duplicate this hormonal effect. For comparative purposes, we also evaluated the influence of these various pharmacologic compounds on the tear volume, the magnitude of lymphocyte infiltration in the submandibular gland, and the extent of mucosal and peripheral lymphadenopathy.
  
  
  METHODS
  Female MRL/MpJ-lpr/lpr mice were administered vehicle, steroids, or immunosuppressive compounds for 21 days after the onset of disease. Lacrimal glands and tears, as well as submandibular glands, spleens, and superior cervical and mesenteric lymph nodes were collected immediately before or after treatment and then processed for analysis.
  
  
  RESULTS
  Our results showed that: (1) the immunosuppressive impact of testosterone on lymphocyte infiltration in lacrimal tissue was reproduced by the administration of 19-nortestosterone or cyclophosphamide, but not by therapy with 17 beta-estradiol, danazol, the experimental steroid Org 4094, cyclosporine A or dexamethasone; (2) treatment with testosterone, 19-nortestosterone, cyclophosphamide, or dexamethasone significantly reduced the extent of inflammation in salivary glands; (3) exposure to cyclophosphamide markedly diminished the size of lymphatic and splenic tissues, whereas glucocorticoid treatment only decreased the weight of superior cervical lymph nodes; and (4) administration of 17 beta-estradiol, Org 4094, or dexamethasone led to a significant decrease in tear volume.
  
  
  CONCLUSIONS
  Overall, these results demonstrate that androgen or cyclophosphamide therapy may successfully ameliorate autoimmune expression in lacrimal and salivary glands of a female mouse model of Sjögren's syndrome.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute, Boston, Massachusetts 02114.
authors.forename: E H
authors.initials: EH
authors.lastname: Sato
authors.forename: D A
authors.initials: DA
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006728:Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000276:immunology; D007766:Lacrimal Apparatus Diseases / Q000188:drug therapy* / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013363:Submandibular Gland / Q000276:immunology; D013666:Tears / Q000276:immunology
chemical_list: D003692:Delayed-Action Preparations; D006728:Hormones; D007166:Immunosuppressive Agents