Labrafil--a new adjuvant for peptide-specific oral tolerance in rat experimental autoimmune uveitis.
Application of soluble antigen via the oral route results in systemic antigen-specific tolerance, a therapeutic approach that has already been used for uveitis patients. In the Lewis rat experimental autoimmune uveitis (EAU) can be induced by active immunisation with retinal antigens such as retinal soluble antigen (S-Ag) or interphotoreceptor retinoid-binding protein (IRBP) and peptides thereof. These normally pathogenic antigens can also be used to induce oral tolerance. In order to optimize oral tolerance induction we analysed the effect of Labrafil M 2125 CS, an orally administrable composition for pharmaceutical use, consisting of fatty acid esters and glycerides and capable of forming micro emulsions. Feeding peptide emulsified in Labrafil M 2125 CS/PBS prior to immunisation significantly improved oral tolerance compared to feeding peptide in PBS only. We observed a delayed onset of disease, reduced intraocular inflammation and less retinal destruction. Application of Labrafil M 2125 CS without tolerogen had no effect. Combined feeding of peptide with Labrafil M 2125 CS even allowed 10-fold reduction of the tolerogenic peptide dose. Furthermore, the effect of Labrafil M 2125 CS upon oral tolerance was dose-dependent, a peptide emulsion containing 0.5-2% Labrafil M 2125 CS achieved a maximal enhancement of oral tolerance induction, suggesting that Labrafil M 2125 CS might be a useful adjuvant to enhance therapeutic use of oral tolerance.
Department of Ophthalmology, Section of Immunobiology, Ludwig-Maximilians-University, Mathildenstr. 8, D-80336 Munich, Germany. maria.diedrichs-moehring@med.uni-muenchen.de
Maria
M
Diedrichs-Möhring
Stephan R
SR
Thurau
Gerhild
G
Wildner
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D005136:Eye Proteins / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005989:Glycerides / Q000008:administration & dosage*; D007108:Immune Tolerance; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D013501:Surface-Active Agents; D014605:Uveitis / Q000517:prevention & control*
D005136:Eye Proteins; D005989:Glycerides; D010446:Peptide Fragments; D013501:Surface-Active Agents; D011092:Polyethylene Glycols