ANDROGEN STIMULATION OF LACRIMAL GLAND-FUNCTION IN MOUSE MODELS OF SJOGRENS-SYNDROME

Sjogren's syndrome, an autoimmune disease that occurs primarily in wom en, causes extensive inflammation and significant dysfunction in the l acrimal gland, and is one of the leading causes of dry eye syndromes t hroughout the world. Recently, our research has shown that androgen tr eatment causes a significant suppression of the immunopathological les ions in lacrimal tissues of female mouse models (MRL/Mp-lpr/lpr [MRL/l pr] and NZB/NZW F1 [F1]) of Sjogren's syndrome. To extend these findin gs, the objective of the present study was to determine whether this a ndrogen-induced anti-inflammatory action may be paralleled by an incre ase in the functional activity of lacrimal glands in these autoimmune mice. Towards this end, we measured the tear levels of immunoglobulin A (IgA), which originates from lacrimal tissue and whose concentration is known to be diminished in mucosal sites in Sjogren's syndrome. For comparative purposes, we also evaluated whether the administration of other steroid hormones or immunosuppressive agents might duplicate po ssible androgen effects on the secretory function of lacrimal tissue. Female MRL/lpr and Fl, as well as non-autoimmune BALB/c, mice were tre ated with vehicle, steroids or immunosuppressive compounds for 17 to 5 4 days after the onset of disease. Lacrimal glands, tears and sera wer e collected immediately before (pretreatment), or after, therapy and p rocessed for the analysis of either tear IgA (enzyme-linked immunosorb ent assay; ELISA) and protein content or the magnitude of lymphocyte i nfiltration (computer-assisted image analysis). Our findings demonstra ted that testosterone treatment stimulated a significant increase in t he concentration and total amount of tear IgA, as well as tear protein , compared to levels in pretreatment or placebo controls. This hormone action was reproduced by exposure to a diverse array of ''anabolic'' and ''androgenic'' androgen analogues, but not by treatment with estra diol, danazol, cyclosporine A, dexamethasone or cyclophosphamide. In c ontrast, only dexamethasone increased serum IgA concentrations. Of par ticular interest is the fact that the androgen control of IgA output b y the lacrimal gland appeared to be independent of this steroid's supp ression of lymphocyte infiltration in lacrimal tissue. Overall, these results show that androgen therapy enhances the functional activity of the lacrimal gland in mouse models of Sjogren's syndrome. (C) 1997 El sevier Science Ltd.