Objectives: Enthesitis-related arthritis (ERA) is associated with the increase in frequency of Th17 cells and synovial fluid IL-17 levels. Recently, IL-15 and IL-18 has been shown to augment and IL-27 to suppress IL-17 production in autoimmune disease, and thus we studied these cytokines in ERA patients.
Methods: Serum samples were collected from 55 patients with ERA, 21 with other categories of JIA and 21 healthy controls. 19 paired synovial fluid samples were also collected from ERA patients. IL-17, IL-23, IL-15, IL-18 and IL-27 levels were measured by ELISA and Th17 frequency was assessed by flow cytometry. IL-23 levels and Th17 frequency was done in subsets of patients.
Results: The median disease duration was 36 months in ERA and 24 months in other JIA subjects. No difference was found in serum levels of IL-17, IL-23, IL-15 and IL-18 between ERA and controls whereas the median IL-27 serum levels were decreased in ERA (107.94 pg/ml (<64-444.40 pg/ml)) as compared to healthy controls (267.28 pg/ml (80.90-492.15 pg/ml); p=0.008). In ERA, synovial fluid levels of IL-17, IL-15 and IL-18 were significantly increased but IL-27 levels were significantly decreased as compared to serum levels. Synovial IL-27 levels correlated negatively with Th17 cell frequency (n=11; r=-0.651, p=0.03).
Conclusions: IL-17 and its supporting cytokines IL-15 and IL-18 are increased whereas its regulatory cytokine IL-27 is decreased in synovial compartment, thus the balance is tilted in favour of IL-17 production. Strategies to increase IL-27 may have therapeutic potential in controlling inflammation at local site.