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Suppression of experimental uveitis with monoclonal antibodies to ICAM-1 and LFA-1
1Department of Ophthalmology, Yokohama City University School of Medicine, Japan.
Insights
Anti-ICAM-1 monoclonal antibody (mAb) 1A29 completely prevented experimental autoimmune uveoretinitis (EAU) in rats, while anti-LFA-1 mAb WT.1 only partially suppressed it. These findings highlight ICAM-1 and LFA-1 pathways in EAU pathogenesis.
Area of Science:
- Immunology
- Ophthalmology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) is crucial for immune responses.
- Lymphocyte function associated antigen-1 (LFA-1) interacts with ICAM-1.
- Experimental autoimmune uveoretinitis (EAU) is an immune-mediated eye disease.
Purpose of the Study:
- To investigate the role of ICAM-1 and LFA-1 in EAU pathogenesis.
- To evaluate the therapeutic potential of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAbs) in EAU.
Main Methods:
- Rats were immunized to induce EAU.
- Rats received intraperitoneal injections of anti-ICAM-1 mAb 1A29, anti-LFA-1 alpha chain mAb WT.1, or control antibodies.
- Clinical and histological examinations assessed inflammation.
- Splenocyte proliferation responses to S-Ag were analyzed.
Main Results:
- Administration of anti-ICAM-1 mAb 1A29 completely prevented EAU development when given from day 0 to day 14.
- Anti-LFA-1 mAb WT.1 only partially suppressed EAU.
- The timing of 1A29 administration was critical; delayed or shortened treatment did not prevent EAU.
Conclusions:
- ICAM-1 and LFA-1 dependent pathways are integral to EAU pathogenesis.
- These pathways are essential for both the induction and progression of EAU.
- Targeting ICAM-1 shows significant therapeutic promise for EAU.
Purpose:
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.