Abstract
Purpose: :
In patients with Vogt-Koyanagi-Harada disease (VKH), the sensitivity to corticosteroid therapy varies among individual patients. Recurrence and longstanding intraocular inflammation may depend on the activity of systemic immune responses. In this study, we analyzed in vitro cytokine production of activated lymphocytes, obtained from VKH patients before the treatment with corticosteroid, and compared the results with clinical data.
Methods: :
Peripheral blood mononuclear cells (PBMC) were isolated from 19 active VKH patients (8 male and 11 female, age 45.4±14.7 yrs) before the administration of corticosteroid. The PBMC were stimulated with concanavalin A (ConA) (1 µg/ml) in the absence or presence of betamethasone (0-1.0 µg/ml). After 24h incubation, supernatants were collected and cytokine concentrations (IFN-gamma, IL-2, IL-4, IL-6, IL-10, IL-17, and TNF-alpha) were measured by flow cytometry or enzyme-linked immunosorbent assay. The results of cytokine production were compared with clinical data and disease course.
Results: :
The patients were divided into two groups by the concentration of IL-17 produced by PBMC stimulated with ConA alone: High IL-17 group (IL-17≥30 pg/ml, 6 patients) or low IL-17 group (IL-17<30 pg/ml, 13 patients). High IL-17 group patients required statistically longer durations of systemic corticosteroid administration (high IL-17 group;76.2±60.2 days, low IL-17 group;22.1±15.5 days) and larger amount of corticosteroid (high IL-17 group;4645.8±1584.6 mg, low IL-17 group;2133.9±1329.8 mg) to achieve best corrected visual acuity (BCVA) of 20/20 or better. The mean age was also higher in high IL-17 group (high IL-17 group;55.8±13.9 yrs, low IL-17 group;40.8±12.9 yrs). There was no statistical difference between the two groups as to BCVA at the first visit and the interval between onset of the disease and the beginning of corticosteroid therapy. Betamethasone suppressed the production of all the cytokines tested in a dose-dependent manner, however there was no relation between suppression level of each cytokine and the clinical data or disease course.
Conclusions: :
In VKH patients, analysis of in vitro IL-17 production by activated lymphocytes may predict the therapeutic effects of systemic corticosteroid treatment.
Keywords: uveitis-clinical/animal model • autoimmune disease • cytokines/chemokines