Involvement of levels of Toll like receptor-4 in monocytes, CD4+ T-lymphocyte subsets, and cytokines in patients with immune thrombocytopenic purpura

Abstract

Introduction: Toll-like receptors have been found to be associated with immune-mediated diseases but it is still not clear whether they play a role in immune thrombocytopenic purpura (ITP), especially TLR4. CD4+ T-lymphocyte abnormalities, including Th17, Th1, Th2, and regulator T cell (Treg), are considered important in ITP. There have been few studies regarding the expression of TLR4 and the relationships between TLR4 and Th17 levels in ITP.

Materials and methods: In this study, we evaluated the expression of TLR4 in monocytes, the plasma concentrations of IL-23, IL-17 and the profiles of Th17, Th1, Th2 cells in 70 patients with ITP and 31 healthy controls. In addition, we evaluated IL-2 and Treg cells in 46 cases of 70 patients with ITP and the same 31 controls.

Results: Higher levels of TLR4 expression, higher relative numbers of Th17 and Th1 cells and lower levels of Treg cells were observed in patients when compared with controls (p=0.001 for TLR4; p<0.001 for Th17; p=0.014 for Th1; p=0.001 for Treg). The levels of IL-23 and IL-2 were increased (p=0.022 for IL-23; p=0.025 for IL-2), the relative levels of Th2 and concentrations of IL-17 were similar across both groups (p=0.446 for Th2; p=0.316 for IL-17). A significant negative correlation was observed between levels of TLR4 and Treg(r=-0.544, p<0.001), but a significantly positive correlation was observed between IL-2 and IL-23 concentration in patients (r=0.441, p=0.004). Neither the correlation between TLR4 and the other CD4(+) T cells and cytokines nor the correlation between the three cytokines and CD4+ T cells was found to be statistically significant.

Conclusions: Our data showed that TLR4, CD4+ T cells (Th1, Th17 and Treg cells) and related cytokines (IL-23, IL-2) may take part in the pathogenesis of ITP. TLR4 may play a role through the TLR4-cytokine-CD4+ T lymphocyte cell pathway.

Keywords: CD4+T lymphocyte subsets; IFN-γ; IL-17; IL-2; IL-23; ITP; T helper 1 cells; T helper17 cells; T helper2 cells; T regulator cells; TLR4; Th1; Th17; Th2; Toll like receptor-4; Treg; immune thrombocytopenia; immune thrombocytopenic purpura; interferon-γ; interleukin-17; interleukin-2; interleukin-23.