Cytokine levels in patients with multiple sclerosis and chronic neuroborreliosis

Abstract

An imbalance in the production of proand anti-inflammatory cytokines plays an important role in the pathogenesis of multiple sclerosis (MS) and chronic neuroborreliosis (CNB).Objective: to perform a comparative analysis of cytokine production in patients with MS and CNB in order to evaluate the differential diagnostic potential of a multiplex assay of the concentration of the most important cytokines.Material and methods. Fifty-seven patients participated in the study. The group of patients with relapsing-remitting MS consisted of 36 individuals (12 men and 24 women), median age – 38.5 [28.0; 48.50] years, MS duration – 9.5 [3.5; 12.5] years. Clinical reactivation of persistent herpesvirus infection (PHVI) was present in 18 (50%) patients. The group of patients with CNB comprised 21 patients (4 men and 17 women) aged 59.0 [52.0; 67.0] years with a disease duration of 2.5 [1.0; 4.0] years. 18 healthy donors were analyzed as controls. The concentrations of 15 cytokines in blood serum: interleukin 1β (IL1β), IL4, IL6, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, interferon γ (IFNγ), tumor necrosis factor α (TNFα), soluble CD40 ligand (sCD40L) were determined by xMAP multiplex technology using reagents produced by Bio-Rad (USA).Results. A significant increase in the levels of IL10 and IL33 (p<0.001) and a decrease in the levels of IL1β, IL17F, IL22, IL25 and TNFα were found in patients with MS compared to controls. In patients with CNB, the levels of IL6, IL22, TNFα and sCD40L were significantly lower than in donors (p<0.05 and p<0.001), and the levels of IL10, IL17A, IL23, IL31, IL33 did not differ from the control. The concentrations of IL1β, IL4, IL17F, IL21, IL25 and IFNγ in patients with CNB were below the detection limit for these analytes. In patients with MS, the concentrations of IL6, IL10, IL17A, IL31, IL33, TNFα and sCD40L were significantly higher than in CNB. In contrast, IL23 levels were higher in CNB than in MS (p<0.01). High levels (M+3σ in the control group) of IL33 occurred significantly more frequently in MS than in CNB (52.8 and 0.0% of cases; p<0.001). In MS, overproduction of IL17A (2.8%), IL17F (5.6%), IL21 (5.6%) and IL31 (13.8%) was found. In CNB, an isolated increase in IL31 concentration was found in 4 (19.4%) patients. In MS with and without PHVI reactivation, the concentrations of IL6, IL10, IL17A, IL31, IL33, TNFα and sCD40L were significantly higher than in CNB; the greatest differences to CNB were found in the group of MS patients with PHVI reactivation. In CNB, IL23 levels were significantly higher than in MS with or without manifestations of PHVI.Conclusion. There are significant differences in the production of proand anti-inflammatory cytokines in patients with MS and CNB, which are due to different etiological factors and characteristics of the immune response. In MS, against the background of an increase in IL10 levels, a concomitant increase in blood serum levels of IL6, IL17A, IL31, IL33, TNFα and sCD40L is characteristic, whereas in CND, with a low concentration of IL10 and most of the above proinflammatory cytokines, high levels of IL23 and an isolated increase in IL31 levels are seen. The differences identified can have practical application in the differential diagnosis between these diseases.

Keywords

• multiple sclerosis
• chronic neuroborreliosis
• cytokines
• herpes