Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40-70%) of cognitive impairment. The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS). Methods The study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients had significantly increased serum concentrations of TNF-alpha and IL-17A and decreased levels of IL-10 compared to the controls (p < 0.05). Negative correlation was found between serum TNF-alpha and SDMT score in patients with disease evolution longer than 10 years (rxy = -0.258 p = 0.033); PASAT and SDMT scores were in negative correlation with concentration of IL-17A (rxy = -0.229 p = 0.004; rxy = -0.166 p = 0.041). Cognitive impairment was established in 46.5% (n = 74) of the patients. Cognitively impaired patients had significantly higher serum IL-17A than cognitively preserved individuals (p = 0.007). Multiple linear regression analysis revealed IL-17A as a significant predictor of cognitive performance in RRMS patients. Conclusion The results from this study suggest that pro-inflammatory cytokines IL-17A and TNF-alpha simultaneously with decreased IL-10 are involved in cognitive deterioration in RRMS.
Keywords: IL-10; IL-17A; Multiple sclerosis; TNF-alpha; cognitive functions; cytokines.