Intranasal administration of denatured type II collagen and its fragments can delay the onset of collagen-induced arthritis.
Collagen-induced arthritis (CIA) is an autoimmune animal model for some types of human rheumatoid arthritis (RA). We have evaluated the effectiveness of intranasal administration of antigen in inhibiting CIA in DBA/1 mice. The intranasal administration of heat-denatured or trypsin-digested bovine type II collagen (CII) before immunization with CII strongly delayed the onset of CIA, whereas administration of native CII did not do so. The mice administered denatured or digested CII possessed much lower titers of anti-CII IgG2a than the control mice, whereas titers of anti-CII IgG1 and IgG2b were unchanged or slightly decreased. Responding to CII and peptides containing immunodominant T cell determinants, lymph node cells from mice administered denatured CII produced less IFN-gamma. These results suggest that intranasal administration of antigen downregulated preferentially Th1-type responses, whereas an enhanced Th2-type response was not observed. We demonstrate that the methods shown here are a possible treatment for rheumatoid arthritis.
Matsumoto
T
T
Department of Applied Biological Chemistry, The University of Tokyo, Tokyo, 113-8657, Japan.
Ametani
A
A
Hachimura
S
S
Iwaya
A
A
Taguchi
Y
Y
Fujita
K
K
Shigehisa
T
T
Kaminogawa
S
S
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D002417:Cattle; D003094:Collagen / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011489:Protein Denaturation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D001323:Autoantibodies; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D007371:Interferon-gamma; D003094:Collagen