Investigation of the role of interleukin 27 in the immune regulation of Treg and Th17 cells in neurosyphilis patients

Introduction:
Neurosyphilis (NS) is known as a sexually transmitted disease that is very difficult to diagnose and its diagnosis is delayed. Some studies have suggested that the level of interleukin (IL)-27 decreases in syphilis patients and the level of IL-17 increases in these patients, and these immunological changes can be a therapeutic target for these patients. The present study aims to evaluate IL-27’s role in the immune regulation of Treg and Th17 cells in NS patients.

Material and methods:
400 documented diagnosed syphilis patients were enrolled to the study and divided into two groups of neurosyphilis (NS) and non-neurosyphilis (S). Also 40 healthy volunteers were enrolled as a healthy control group (C). Peripheral blood mononuclear cells (PBMCs) from peripheral blood and cerebrospinal fluid (CSF) by lumbar puncture were collected as samples. mRNA expression and level of IL-27, IL-17, Th17, IL-17-producing CD4⁺ T cells and also protein concentration and VDRL of CSF were investigated. To obtain proposed results, flow cytometry, RT-PCR and ELISA were used.

Results:
The mRNA expression of IL-27 in PBMCs declined significantly in NS patients compared to healthy controls (p = 0.002) and S patients (p = 0.005) and decreased significantly in CSF of NS patients in comparison to healthy controls (p = 0.002) and S patients (p = 0.003). The frequency of IL-17-producing CD4⁺ T cells increased significantly in PBMCs of NS patients in comparison to healthy controls (p = 0.004) and S patients (p = 0.004). This frequency also increased significantly in CSF of NS patients compared to C (p = 0.007) and S patients (p = 0.003). Adding rIL-27 significantly prevented the frequency of IL-17-producing CD4⁺ T cells from naïve CD4⁺ T cells under Th17 polarizing conditions from NS patients (p = 0.043), C (p = 0.043), and S patients (p = 0.002) in PBMCs, and also 0.03, 0.02 and 0.03 respectively for NS, S and C of CSF. The results revealed a significant negative relationship between CSF protein and VDRL concentrations and CSF IL-27 levels.

Conclusions:
This study confirms previous efforts on the critical role of IL-17 in NS. Also, it supports other results on the inhibitory effects of IL-27 on the therapeutic potential of IL-27 in NS and the inflammation process.