Correlation between IL-17A/F, IL-23, IL-35 and IL-12/-23 (p40) levels in peripheral blood lymphocyte cultures and disease activity in Behcet’s patients

Abstract

Behcet's disease is a chronic multisystemic disease with remissions and relapses. Several studies have shown that immune mechanisms play an important role in the development of the disease. In order to assess the association of disease activity with IL-17A/F, IL-23, IL-12/23 (p40) and IL-35 expression, we aimed to investigate production of these cytokines in peripheral blood mononuclear cells (PBMCs) from Behcet's patients and normal controls. Furthermore, we included Systemic Lupus Erythematosus (SLE) as disease control to evaluate the specificity of our data for immunopathogenesis of BD. Totally 15 active, 15 inactive Behcet's patients, 12 active and 12 inactive SLE patients and 12 healthy volunteers were enrolled in the study. Peripheral blood mononuclear cells were separated, lymphocyte cultures were performed and IL-17A/F, IL-12/23 p(40), IL-23, IL-35 cytokine levels were measured by ELISA in culture supernatants in the presence or absence of phytohemagglutinin (PHA) on time-dependent manner. IL-17 A/F levels increased parallel to IL-23 levels in Behcet's and SLE patients. Compared to healthy controls, IL-17 A/F levels were higher in active Behcet's and SLE patients; on the contrary, levels of IL-35 were lower. IL-17A/F, IL-12/23 (p40) and IL-23 levels were detectable most frequently in active Behcet's patients followed by active SLE patients. Our results indicate that IL-17 A/F, IL-23 and IL-12/23 (p40) may play role in the immunopathogenesis of BD so as Th17 and Th1 cell responses. Since IL-35 levels were lower in active Behcet's patients compared to inactive patients and healthy controls, there may be a plasticity between Th17 and Treg cells according to the state of disease activity.

Immunopathogenesis of Behcet's Disease

“…Therefore, IL-23 plays an important role in the expansion and survival of Th17 cells. High levels of IL-23 have been reported in PBMCs from active BD patients (52, 58). These results suggest that the serum IL-17A/F levels parallel the IL-23 levels in patients with active BD, that the active inflammatory state may lead to the differentiation of Th17 cells, and that the IL-17/23 axis has a significant role in mediating inflammatory responses in BD.…”

“…Sonmez et al reported that a low level of the Treg cytokine IL-35 was negatively correlated with the number of Th17 and Treg cells. The level of IL-35 in patients with inactive BD and healthy controls was higher than that in patients with active BD, a finding that could be explained by the plasticity between Th17 cells and Treg cells (58).…”

Interleukin 35: an overview

“…35 Decreased serum levels of IL-35 in patients with the active stage of Behcet disease compared to inactive Behcet patients and healthy controls might be a sign of the flexibility of T reg lymphocytes depending on the stage of the disease. 36…”

The Role of Th17 Cells in the Pathogenesis of Behçet’s Disease

“…Foxp3 inhibits Th17 differentiation by antagonizing the RORγt function [62]. Sonmez et al [63] reported that IL-17A/F levels increased parallel to IL-23 levels in BD and IL-35 levels were lower in active BD patients than the inactive BD patients, which may be a plasticity between Th17 and Treg cells according to the state of disease activity.…”

“…Liu et al reported that significantly higher levels of IL-17 are detected in active BD patients and stimulation with IFN-α decrease IL-17 production [17]. In vitro study showed that IFN-α does not directly regulate the Th1/Th17 balance in BD but rather promotes a regulatory Th1 response through IL-10 secretion [63]. IFN-α activity was mediated via STAT2 phosphorylation [17].…”