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Clinical Significance of Serum IL-15 and IL-17 in Relation to Rheumatoid Arthritis' Severity and Activity

ABSTRACT: In this study, we measured serum IL-15 and IL-17 levels in a cohort of patients with rheumatoid arthritis (RA) in order to assess their relevance with the disease’s activity and severity, as well as delineating any potential correlation with various clinical and laboratory parameters routinely used to evaluate RA disease activity and severity. Peripheral blood samples were collected from all recruits and used for the estimation of serum IL-15, IL-17, anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) and C-reactive protein (CRP) as well as erythrocyte sedimentation rate (ESR). RA activity and severity were also determined using disease activity score 28 (DAS28) as well as tender joint count (TJC) and swollen joint count (SJC) respectively. RA patients showed significantly higher mean serum IL-15 and IL-17 levels than controls (P< 0.01). In addition, IL-15 and IL-17 serum levels were found to be significantly higher in RA patient with active disease in comparison to those in remission. Patient with high disease activity showed significantly higher mean serum IL-17 levels than moderate and low disease activity groups while no significant difference was observed in the mean serum IL-15 levels among the three groups. No significant correlation was noted between IL-15 serum level and RF, CRP, ESR and anti-CCP but it was significantly correlated with DAS28, TJC and SJC. Significant positive correlations of serum IL-17 level were found with ESR, CRP, anti-CCP, DAS28, TJC, and SJC, as well as a direct significant correlation between IL-15 and IL-17 serum levels.

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST823 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundPatients with rheumatoid arthritis (RA) have increased levels of interleukin-18 (IL-18) and decreased levels of IL-18 binding protein (IL-18BP) in the serum and synovial fluid (SF) compared to those in patients with osteoarthritis (OA) or in healthy controls. In this study, we evaluated the effects of IL-18BP on osteoclastogenesis and T cell differentiation in RA in vitro.MethodsSerum and SF of patients with RA and OA were collected to compare IL-18 and IL-18BP levels by the enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) and SF mononuclear cells (SFMCs) of RA patients were cultured under type 17 helper T cell (Th17) polarisation conditions with or without IL-18BP. In addition, PBMCs were cultured in the presence of receptor activator of nuclear factor kappa-Β ligand (RANKL) or IL-17A with or without IL-18BP, and tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction for expression levels of osteoclast-related genes were performed.ResultsIL-18 levels were higher in the serum and SF of patients with RA, whereas IL-18BP was lower in the SF of patients with RA than in the control group. Treatment of patients' PBMCs with IL-18BP decreased the differentiation of CD4+ IL-17A+ and CD4+ RANKL+ T cells, whereas the differentiation of CD4+CD25highFOXP3+ T cell population increased in a dose-dependent manner. These changes in CD4+ T cell differentiation were also observed in the SFMCs of patients with RA. The levels IL-17A and soluble RANKL in the culture medium were significantly decreased by IL-18BP. IL-18BP administration decreased TRAP+ cell counts in a dose-dependent manner on the background of stimulation with RANKL-and IL-17A. In addition, expression levels of TRAP, NFATC1, CTSK, and TNFRSF11A (RANK) genes were lower in the IL-18BP treated cells.ConclusionWe showed that IL-18BP can rectify the Th17/Treg imbalance and decrease IL-17-induced osteoclastogenesis in PBMCs from patients with RA. Therefore, IL-18BP may have therapeutic potential for RA treatment.

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Clinical Significance of Serum IL-15 and IL-17 in Relation to Rheumatoid Arthritis' Severity and Activity

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