Background
Vasoactive intestinal peptide (VIP), a neuropeptide that is known tobe present in lymphoid tissue microenvironments, shows prominent anti-inflammatoryactions.
Objective
To examine the potential effect of VIP on the development of experimentalautoimmune uveoretinitis (EAU).
Design
We immunized C57BL/6 mice with human interphotoreceptor retinoid-bindingprotein peptide 1-20 (h-IRBP peptide). Vasoactive intestinal peptide was administeredintraperitoneally on alternate days until day 21 after immunization (entiregroup). In some cases, VIP was injected at different time points after theinduction of immunity with h-IRBP peptide (efferent group). In each experiment,a control group of mice was injected with phosphate-buffered saline insteadof VIP. Development of EAU was evaluated by means of histological examinationon day 21 after immunization. Furthermore, we determined whether intravenousinjection of peritoneal exudate cells cultured with VIP overnight in vitroabrogated EAU. We analyzed delayed hypersensitivity for h-IRBP peptide andthe occurrence and severity of EAU using evaluation of histopathological sectionsfor inflammatory ocular disease.
Results
Treatment with VIP suppressed the expression of delayed hypersensitivityresponses to h-IRBP peptide significantly (positive control vs entire group, P = .02; positive control vs efferent group, P<.001). Mice treated with VIP (n = 10) showed a lower occurrence(40%) and decreased severity of EAU (entire group mean score, 0.3; medianscore, 0) compared with untreated mice (occurrence, 80%; mean score, 0.85;median score, 0.75), as assessed by histopathological analyses (P = .049). Suppressive effects of VIP on EAU were also observed, evenwhen VIP was administered on days 8 through 20 after immunization (efferentgroup [n = 9] occurrence, 11%; mean score, 0.1; median score, 0) (P = .003). Moreover, expression of EAU was significantly suppressedwhen the animals were pretreated with peritoneal exudate cells pulsed withh-IRBP in the presence of VIP (control mean score, 1.2; median score, 1.0;occurrence, 80% [n = 10]) compared with the VIP-treatment group (mean score,0.3; median score, 0; occurrence, 30% [n = 10]) (P =.004). In addition, VIP-treated peritoneal exudate cells generated regulatorT cells in the spleens of recipient mice that were able to interfere withthe development of EAU (control group mean score, 0.5; median score, 0.5;occurrence, 63% [n = 8]) compared with the VIP-treatment group (mean score,0.08; median score, 0; occurrence, 17% [n = 6]) (P =.08).
Conclusion
Treatment with VIP is a highly effective therapy to suppress EAU.
Clinical Relevance
As a result of its efficacy in preventing EAU, VIP might be consideredas a novel therapeutic modality for human uveitis.