Comparative Effects of Sertraline, Methotrexate, and Biologic Therapies on Circulating Inflammatory and Neurotrophic Mediators and Striatal Gene Expression in Collagen-Induced Arthritis.

Rheumatoid arthritis is often accompanied by neuropsychiatric manifestations, suggesting interactions between systemic inflammation and the central nervous system. This study evaluated the effects of sertraline, compared with methotrexate, infliximab, and tocilizumab, on circulating inflammatory and neurotrophic mediators and the striatal expression of selected CNS-related genes in collagen-induced arthritis. Male Wistar rats were assigned to seven groups: adjuvant control, untreated arthritis, methotrexate, sertraline, methotrexate plus sertraline, infliximab, or tocilizumab. At week 12, circulating IL-6, IL-15, IL-10, BDNF, myostatin, and irisin were measured, and striatal BDNF, IL-1β, and GFAP expression was assessed by quantitative real-time PCR. IL-6 concentrations differed between groups, with the lowest values after infliximab treatment and the highest in untreated arthritic rats and animals receiving methotrexate plus sertraline or tocilizumab. IL-15 was highest in untreated arthritis, whereas IL-10 was generally higher in treated groups and peaked after tocilizumab. The IL-6/IL-10 ratio was lower in all treated groups than in untreated arthritis, with the most pronounced reduction observed after infliximab. Circulating BDNF concentrations were highest in the infliximab- and tocilizumab-treated groups. Striatal BDNF expression differed significantly between groups, whereas no significant between-group differences were detected in striatal GFAP or IL-1β expression. No significant between-group differences were observed for circulating myostatin or irisin. Sertraline-containing regimens were associated with lower IL-6/IL-10 ratios than untreated arthritis, whereas infliximab and tocilizumab were associated with the most pronounced changes in systemic inflammatory and neurotrophic parameters.