Use of topical cyclosporin A in a primary Sjögren's syndrome mouse model

Invest Ophthalmol Vis Sci. 1998 Aug;39(9):1551-9.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Cyclosporine / administration & dosage*
  • DNA Primers / chemistry
  • Disease Models, Animal*
  • Female
  • Flow Cytometry
  • Hyaluronan Receptors / metabolism
  • Immunoenzyme Techniques
  • Immunosuppressive Agents / administration & dosage*
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Lacrimal Apparatus / drug effects
  • Lacrimal Apparatus / metabolism
  • Lacrimal Apparatus / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Ophthalmic Solutions
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Sjogren's Syndrome / metabolism
  • Sjogren's Syndrome / pathology
  • Sjogren's Syndrome / prevention & control*
  • Submandibular Gland / drug effects
  • Submandibular Gland / metabolism
  • Submandibular Gland / pathology

Substances

  • DNA Primers
  • Hyaluronan Receptors
  • Immunosuppressive Agents
  • Interleukin-2
  • Ophthalmic Solutions
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • Cyclosporine