COMPARATIVE INFLUENCE OF STEROID-HORMONES AND IMMUNOSUPPRESSIVE AGENTS ON AUTOIMMUNE EXPRESSION IN LACRIMAL GLANDS OF A FEMALE MOUSE MODEL OF SJOGRENS-SYNDROME

Purpose. Previous research has demonstrated that testosterone therapy causes a profound suppression of autoimmune disease in lacrimal glands of female mouse models of Sjogren's syndrome. The aim of the present study was to determine whether other anabolic androgens, nonandrogenic steroids, or immunosuppressive agents might duplicate this hormonal e ffect. For comparative purposes, we also evaluated the influence of th ese 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 co mpounds for 21 days after the onset of disease. Lacrimal glands and te ars, as well as submandibular glands, spleens, and superior cervical a nd mesenteric lymph nodes were collected immediately before or after t reatment and then processed for analysis. Results. Our results showed that: (1) the immunosuppressive impact of testosterone on lymphocyte i nfiltration in lacrimal tissue was reproduced by the administration of 19-nortestosterone or cyclophosphamide, but not by therapy with 17 be ta-estradiol, danazol, the experimental steroid Org 4094, cyclosporine A or dexamethasone; (2) treatment with testosterone, 19-nortestostero ne, cyclophosphamide, or dexamethasone significantly reduced the exten t of inflammation in salivary glands; (3) exposure to cyclophosphamide markedly diminished the size of lymphatic and splenic tissues, wherea s glucocorticoid treatment only decreased the weight of superior cervi cal lymph nodes; and (4) administration of 17 beta-estradiol, Org 4094 , or dexamethasone led to a significant decrease in tear volume. Concl usions. Overall, these results demonstrate that androgen or cyclophosp hamide therapy may successfully ameliorate autoimmune expression in la crimal and salivary glands of a female mouse model of Sjogren's syndro me.