Use of topical cyclosporin A in a primary Sjögren's syndrome mouse model.
OBJECTIVE
A new animal model, the NFS/sld mutant mouse, was used for primary Sjögren's syndrome to investigate the efficacy of topical and systemic cyclosporin A (CyA) in preventing inflammation of the exocrine glands.


METHODS
Cyclosporin A was applied topically (0.01% and 0.1%, three times a day) or administered orally (10 mg/kg and 100 mg/kg, once a day) to mice from 6 to 16 weeks of age, after which the mice were killed.


RESULTS
Topical CyA reduced lacrimal gland and submandibular gland inflammation without causing pathologic changes in other organs. Flow cytometry showed that CD44 expression of CD4 T cells from the submandibular lymph nodes was downregulated, whereas that of Mel14+ was upregulated. Using a reverse transcription-polymerase chain reaction assay, we determined that topical CyA significantly decreased the expression of mRNA of IL-2 and T-cell receptor-constant beta-chain.


CONCLUSIONS
Topical CyA may be clinically useful in reducing the lymphocyte infiltration of lacrimal glands associated with Sjögren's syndrome.
Department of Ophthalmology, and the Oral Health Science Center, Tokyo Dental College, Chiba, Japan.
K
K
Tsubota
I
I
Saito
N
N
Ishimaru
Y
Y
Hayashi
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage*; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009883:Ophthalmic Solutions; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D017931:DNA Primers; D018960:Hyaluronan Receptors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine