Inhibition of very late antigen-4 and leukocyte function-associated antigen-1 in experimental autoimmune uveoretinitis.
B10.RIII mice were immunized with interphotoreceptor retinoid binding protein peptide to induce uveitis. Mice were injected intraperitoneally with anti-very late antigen-4 (VLA-4), anti-leukocyte function-associated antigen-1 (LFA-1), or a control Ab every other day from Day 5 to Day 13 post-immunization. The eyes and spleens were harvested on Day 14 or 28. The eyes were used for histologic/cytokine mRNA expression analyses. The spleens were used for Ag-recall cytokine production assays and intracellular cytokine assays. Treatment with both Abs led to a profoundly significant reduction in severity of uveitis and cytokine mRNA expression in the eye. However, cytokine production by splenocytes was significantly upregulated. Discontinuation of Ab treatment led to an increase in uveitis severity and cytokine mRNA expression in the eye, but led to a decrease in cytokine production and intracellular IFN-γ(+) and IL-17A(+)cytokine profile by splenocytes. Thus, blockade of these molecules using specific Abs may be a therapeutic option for patients with uveitis; however, such treatment must be continued.
Department of Ophthalmology, Kochi Medical School, Nankoku City, Kochi 783-8505, Japan.
Waka
W
Ishida
Department of Ophthalmology, Kochi Medical School, Nankoku City, Kochi 783-8505, Japan.
Yosuke
Y
Harada
Department of Ophthalmology, Kochi Medical School, Nankoku City, Kochi 783-8505, Japan.
Ken
K
Fukuda
Department of Ophthalmology, Kochi Medical School, Nankoku City, Kochi 783-8505, Japan.
Osamu
O
Taguchi
Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Hideo
H
Yagita
Department of Ophthalmology, Kochi Medical School, Nankoku City, Kochi 783-8505, Japan. Electronic address: fukusima@kochi-u.ac.jp.
Atsuki
A
Fukushima
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger
Antibodies (Abs); Experimental autoimmune uveoretinitis (EAU); Leukocyte function-associated antigen-1 (LFA-1); Mouse; Very late antigen-4 (VLA-4)