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Objective: Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE., Methods: Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels., Results: Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels., Conclusion: SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.

Objective: To investigate the levels of the T helper (Th)17-related cytokines interleukin 17A (IL-17A), IL-21, and IL-23 and their association with disease activity in rheumatoid arthritis (RA)., Methods: In a longitudinal sample set from patients with early RA (< 6 months; n = 40), we measured the plasma cytokine levels of IL-17A, IL-21, and IL-23 and analyzed for correlation with disease activity in 28 joints (Disease Activity Score 28-joint count; DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and total Sharp score (TSS). In a transverse sample set of patients with chronic RA (> 8 years), using paired peripheral blood mononuclear cells and synovial fluid mononuclear cells, we investigated the cellular expression of IL-17A, IL-21, and IL-23R., Results: Patients with early-stage RA had significantly increased plasma levels of IL-21 and IL-23, but not IL-17A, compared to patients with chronic RA and healthy volunteer controls. Plasma levels of IL-21 and IL-23 after 12 months of treatment correlated with DAS28 and ESR, but not to TSS. Changes in IL-23 plasma levels from time of diagnosis to 12 months correlated with change in DAS28 and with TSS scores at 2 years. The numbers of CD4+ T cells producing IL-21 were significantly increased in the synovial fluid of patients with chronic RA, with only marginal coexpression of IL-21 and IL-17A., Conclusion: Our results show a significant association between plasma levels of IL-21 and IL-23 and disease activity in RA, supporting the hypothesis that IL-21 and IL-23 are important pathogenic factors of this disease.

Objective: A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA., Methods: The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ss (IL-1ss), IL-6, IL-21, IL-23, and transforming growth factor ss (TGF-ss), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml., Results: There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-gamma+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ss (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ss were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable., Conclusion: In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ss and IL-6 in SF may be responsible for increased Th17 cells.

Objective: The relationship between systemic sclerosis (SSc) and interleukin 23 (IL-23), a cytokine associated with the differentiation of T lymphocytes, is unknown. We investigated serum IL-23 levels and their clinical association in patients with SSc., Methods: Serum IL-23 levels were examined by ELISA in 63 patients with SSc, 15 patients with systemic lupus erythematosus (SLE), and 31 healthy individuals. SSc patients comprised 25 with limited cutaneous SSc and 38 with diffuse cutaneous SSc., Results: Serum IL-23 levels were significantly elevated in SSc patients compared to patients with SLE (p < 0.05) and controls (p < 0.005). Elevated serum IL-23 levels were associated with the disease duration (p < 0.05) and the prevalence of pulmonary fibrosis (p < 0.05), although they were not associated with other clinical features, including the extent of skin sclerosis or the severity of pulmonary fibrosis., Conclusion: The results suggest that IL-23 is associated with induction of SSc and that blockade of IL-23 can be a potential therapeutic strategy in early SSc.