Cyclosporine therapy suppresses ocular and lacrimal gland disease in MRL/Mp-lpr/lpr mice.

Abstract

PURPOSE:

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.

• Authors: D A Jabs, B Lee, C L Burek, A M Saboori, R A Prendergast
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 37 Issue 2 Pg. 377-83 (Feb 1996) ISSN: 0146-0404 [Print] United States
• PMID: 8603842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Antinuclear
• Immunoglobulin G
• Immunosuppressive Agents
• Cyclosporine
• DNA

Topics

• Animals
• Antibodies, Antinuclear (analysis)
• Autoimmune Diseases (immunology, pathology, prevention & control)
• Choroiditis (immunology, pathology, prevention & control)
• Cyclosporine (blood, therapeutic use)
• DNA (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glomerulonephritis (pathology, prevention & control)
• Immunoglobulin G (analysis)
• Immunosuppressive Agents (blood, therapeutic use)
• Injections, Intraperitoneal
• Lacrimal Apparatus (drug effects, pathology)
• Lacrimal Apparatus Diseases (immunology, pathology, prevention & control)
• Lymph Nodes (drug effects, pathology)
• Mice
• Mice, Mutant Strains
• Scleritis (immunology, pathology, prevention & control)
• Sjogren's Syndrome (immunology, pathology, prevention & control)