Suppression of experimental uveitis with monoclonal antibodies to ICAM-1 and LFA-1.
OBJECTIVE
Intercellular adhesion molecule-1 (ICAM-1), which is one of the ligands for lymphocyte function associated antigen-1 (LFA-1), plays an important role in immune responses. To examine whether ICAM-1 and LFA-1 are involved in the pathogenesis of experimental autoimmune uveoretinitis (EAU), the authors investigated the therapeutic effect of anti-ICAM-1 monoclonal antibody (mAb) 1A29 and anti-LFA-1 alpha chain mAb WT.1 on retinal soluble antigen (S-Ag) and Freund's complete adjuvant (FCA)-induced EAU in rats.


METHODS
After immunization with S-Ag and FCA, rats were intraperitoneally injected with a monoclonal antibody, anti-ICAM-1 mAb 1A29 or anti-LFA-1 alpha chain mAb or control Ab, at 1.0 mg/kg body weight, according to the treatment schedule. Inflammation was examined clinically and histologically. Proliferative responses of splenocytes to S-Ag were also examined.


RESULTS
The development of EAU could be completely prevented by the administration of 1A29, 1.0 mg/kg, twice a week from day 0 to day 14, but was only partially suppressed by WT.1. However, semiweekly administration of 1A29 from day 0 to day 7, or from day 10 to day 17, did not suppress EAU.


CONCLUSIONS
These findings indicate that ICAM-1, LFA-1-dependent pathways are involved in the pathogenesis of EAU. In addition, these pathways seem to be required for both the induction and the development of this disease.
Uchio
E
E
Department of Ophthalmology, Yokohama City University School of Medicine, Japan.
Kijima
M
M
Tanaka
S
S
Ohno
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000941:Antigens; D019393:Arrestin; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004195:Disease Models, Animal; D005136:Eye Proteins; D005620:Freund's Adjuvant; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000941:Antigens; D019393:Arrestin; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D005620:Freund's Adjuvant