Total dose and frequency of administration critically affect success of nasal mucosal tolerance induction

Hui-Rong Jiang, Neil Taylor, Linda Duncan, Andrew D Dick, John V Forrester

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

AIMS: Nasal tolerance induction with autoantigens can effectively protect against a variety of experimental models of autoimmune disease. The aims of this study were to characterise the dosage and kinetics of inhibition of experimental autoimmune uveoretinitis (EAU) via intranasal administration of the uveitogenic antigen interphotoreceptor retinal binding protein (IRBP) in the murine model of IRBP induced EAU.

METHODS: B10RIII mice were tolerised by intranasal administration of IRBP either with a long term multiple low dose or a short term/high dosing regimen before subcutaneous immunisation with IRBP in complete Freund's adjuvant (CFA). On day 15 post-immunisation, mice were killed and eyes were removed for histological examination and quantification of inflammatory cell infiltration and degree of target organ (rod outer segment, ROS) destruction.

RESULTS: Nasal administration of multiple low doses of IRBP (1 microg or 3 microg IRBP per mouse per day for 10 days) significantly protected mice from IRBP induced EAU. Short term/high dose regimens were only effective when given either as a single or, at most, as two consecutive doses (40 microg per dose). Multiple doses in the range of 45-120 microg over 3 days afforded no protection.

CONCLUSIONS: These results indicate that both dose and frequency of intranasal antigen administration are pivotal to tolerance induction and subsequent suppression of T cell mediated autoimmune disease.

LanguageEnglish
Pages739-744
Number of pages6
JournalBritish Journal of Ophthalmology
Volume85
Issue number6
DOIs
Publication statusPublished - 1 Jun 2001

Fingerprint

Nose
Carrier Proteins
Intranasal Administration
Autoimmune Diseases
Immunization
Rod Cell Outer Segment
Antigens
Freund's Adjuvant
Autoantigens
Theoretical Models
T-Lymphocytes

Keywords

  • administration, intranasal
  • animals
  • autoantigens
  • autoimmune diseases
  • carrier proteins
  • disease models, animal
  • Freund's adjuvant
  • immune tolerance
  • immunization
  • male
  • mice
  • mice, inbred strains
  • statistics, nonparametric
  • treatment outcome
  • uveitis

Cite this

Jiang, Hui-Rong ; Taylor, Neil ; Duncan, Linda ; Dick, Andrew D ; Forrester, John V. / Total dose and frequency of administration critically affect success of nasal mucosal tolerance induction. In: British Journal of Ophthalmology. 2001 ; Vol. 85, No. 6. pp. 739-744.
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Total dose and frequency of administration critically affect success of nasal mucosal tolerance induction. / Jiang, Hui-Rong; Taylor, Neil; Duncan, Linda; Dick, Andrew D; Forrester, John V.

In: British Journal of Ophthalmology, Vol. 85, No. 6, 01.06.2001, p. 739-744.

Research output: Contribution to journalArticle

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