Use of topical cyclosporinea in primary sjogren's syndrome moush model

PjiAliytsCJ In autoimmune lesions, infiltratingT cells have been reported to express activation molecules, especially II.-2, which can be suppresed b> cyclosporine A (CSA). We have used a new animal model for primary Sjogren's syndrome, (he NFS/sld mutant mouse, to investi gate the efficacy of topical and systemic CSA in prevent ing inflammation of the exocrine glands. Methods: CSA was given topically (0.01 7, and0.1<7( CSA. 2 ul 3 times a day, N=46) or orally ( 10mg/kg, and 100 mg/kg. once a dav, N-23 ) from 6 weeks to 16 weeks of age, at which time the mice were sacrificed. Results: Topical CSA reduced lacrimal gland inflammation without causing an\ pathologic changes in other organs. Flow cy tome trie analysis showed t hat CD44 expression of CD4 T cells from the submandibular lymph nodes was downregtilaied, w hereas that of Mel 14+ and CÜ45RB+ CD4T cells was upregulated. We also found that topical CSA significantly decreased the expression of IL.-2 mRNA and T cell receptor constant j3 -chain in lacrimal glands. In contrast, systemic CSA caused increased inflammation of the lacrimal gland, thyroid, pancrease. bronchus, and kidney. Conclusion: This study suggests that topical CSA may be clinically useful in reducing lymphocyte infiltration of iacrimal glands associated w ith Sjogren s syndrome.