Abstract
Purpose :
Interferon alpha (IFN-a) is a successful therapy of ocular Behçet's disease, but the underlying immune mechanisms are not yet fully understood. To further elucidate the therapeutic mechanisms we investigated the effect of IFN-a on leukocyte populations in two experimental rat models of relapsing and monophasic/chronic uveitis (EAU).
Methods :
Uveitis was induced by immunization with either retinal S-Ag peptide PDSAg (monophasic/chronic EAU) or IRBP-peptide R14 (relapsing EAU). Recombinant human IFN-alpha was subcutaneously injected every day or every other day at different doses (1000 or 5000 IU) starting from different time points. Uveitis was graded clinically and histologically. Peritoneal exudate cells (PEC), lymph node (LN) cells and peripheral blood lymphocytes (PBL) were investigated for surface markers and cytokine expression by FACS-analysis
Results :
Preventive treatment with IFN-alpha starting with immunization significantly decreased the primary inflammation as well as relapses of R14-induced EAU, while PDSAg-induced, monophasic disease was deteriorated. Lymph node cells of PDSAg-immunized, IFN-a-treated rats revealed more TCR+ cells expressing IFN-g, IL-17 or both, and less TCR+ cells producing IL-10 compared to the PBS-treated control group. IFN-a treatment decreased cell populations expressing CD161 in PDSAg-immunized Lewis rats, whereas in R14-induced EAU an increase in CD161+ cells was seen in PEC, LN and PBL.
Conclusions :
IFN-a-treatment had different effects on relapsing and monophasic rat uveitis models. The deterioration of PDSAg-induced EAU by IFN-a-treatment might be due to an increase in leukocyte populations expressing inflammatory cytokines, and cells expressing CD161 might have a regulatory effect.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.