Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechçet's disease; soluble TNFR-75 as a biological marker of disease activity

Abstract

Objective: To analyze the levels of the T cell regulatory cytokines interleukin 10 (IL-10) and IL-12 in plasma of patients with Behçet's disease (BD), and to assess the value of cytokines and cytokine antagonists as biological markers of disease activity.

Methods: Sera/plasma of 66 consecutive outpatients with established diagnosis of BD were analyzed for the presence of IL-2R, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble (s) TNF receptor (R)-55, sTNFR-75, IL-10, and IL-12 using immunological methods. Additional laboratory measurements included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Data from the history and clinical examination were recorded to correlate cytokine levels with clinical markers of disease activity.

Results: 18 patients had inactive (Group I), 36 had mildly active (Group II), and 12 patients had active BD (Group III). IL-10 was elevated in 42 plasma samples (64%). The percentage of samples containing IL-10 and the median levels of IL-10 of the 3 patient groups did not differ significantly. IL-12 was detectable in plasma of 9 patients: One from Group I (5%), 3 from Group II (8%), and 5 from Group III (41%). IL-12 correlated with disease activity (difference between Groups I and III, p = 0.02, between Groups II and III, p = 0.008). ESR in patients with active disease and mildly active disease was significantly higher than values in patients with inactive disease (p = 0.03, p = 0.02, respectively), while median CRP levels were significantly different between Group I and Group III only (p = 0.006). sTNFR-75 levels were significantly different between Groups II and III (p = 0.003) and between Groups I and III (p = 0.008).

Conclusion: The elevation of plasma IL-10 in the majority of patients and the correlation of IL-12 plasma levels with disease activity suggest a pathogenic role of a TH1-type immune response in active disease. In addition, the correlation of sTNFR-75 levels with disease activity indicates that sTNFR-75 may serve as a biological marker of disease activity in BD.