Cyclosporine therapy suppresses ocular and lacrimal gland disease in MRL/Mp-lpr/lpr mice.
OBJECTIVE
MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune disease characterized by lymphoproliferation, vasculitis, glomerulonephritis, autoantibody production, and ocular and lacrimal gland inflammation. Lacrimal gland lesions in MRL/lpr mice are a model for the human disorder Sjögren's syndrome. The target organ lesions in MRL/lpr mice, including those in the eye and lacrimal gland, are composed largely of CD4+ T cells, with lesser numbers of CD8+ T cells and B cells. Cyclosporine therapy was evaluated for its effect on the autoimmune disease, particularly in the eye and lacrimal gland.


METHODS
MRL/lpr mice were administered cyclosporine intraperitoneally at a dosage of 2 mg daily from age 1 to 5 months. Animals were killed at 5 months and evaluated for the presence of autoimmune disease. Control groups consisted of animals given daily injections with either saline or the cyclosporine diluent.


RESULTS
Cyclosporine therapy was effective in reducing the ocular and lacrimal gland disease. Intraocular inflammation was present in 73% of control animals but in only 15% of cyclosporine-treated animals (P < 0.003). Multifocal lacrimal gland inflammatory infiltrates were present in 100% of controls but in only 23% of cyclosporine-treated animals (P < 0.0001). Mean percent area involved by lacrimal gland inflammation was reduced from 19.7% to 4.7% by cyclosporine therapy (P = 0.0003). Systemic autoimmune disease manifestations, including lymphoproliferation, vasculitis, glomerulonephritis, and serologic abnormalities, also were improved.


CONCLUSIONS
Chronic cyclosporine therapy, started at an early age, is effective in controlling the autoimmune disease in MRL/lpr mice, including the ocular and lacrimal gland lesions.
Jabs
D A
DA
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Lee
B
B
Burek
C L
CL
Saboori
A M
AM
Prendergast
R A
RA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002833:Choroiditis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000032:analysis; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000473:pathology; D007766:Lacrimal Apparatus Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D015423:Scleritis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004247:DNA