First line therapy for multiple sclerosis: cytokine levels and the impact of herpesvirus infection

The effects of the disease modifying drugs (DMDs) for multiple sclerosis (MS), interferon beta (IFNβ) and glatiramer acetate (GA), on the cytokine levels of individuals with MS are poorly understood. The effects of persistent herpesvirus infection (PHVI) on the cytokine production during treatment with DMDs for MS have not been identified. The role of cytokines and PHVI in the development of the treatment-related adverse events (AEs) has not been determined. The study was aimed to assess serum cytokine levels in patients with MS treated or not treated with DMDs for MS, and to determine the relationships between the cytokine levels, herpesvirus infection, and AEs. A total of 36 patients (12 males and 24 females, median age 38.50 (28.00; 48.50) years) with relapsing-remitting MS (criteria by McDonald, 2010) were examined. PHVI reactivation was observed in 18 individuals; in 10 of them it was associated with the history of the virus-associated exacerbation (VAE) of MS or VAE detected during assessment. A total of 30 patients were treated with DMDs for MS: 16 individuals with IFNβ, 14 individuals with GA. Systemic AEs were reported in 9 individuals. Serum levels of 15 cytokines were determined using the xMAP multiplex technique. Patients with MS showed a significant increase in the levels of IL10 (p < 0.01) and IL33 (p < 0.001) relative to donors when treated or not treated with DMDs for MS; the increase in IL31 levels was reported only in naïve patients (p < 0.05). At the same time, individuals with MS had low levels of IL1β, IL17F, IL22, IL25, IL23, and TNFα (p < 0.01). We revealed no differences in cytokine levels in the context of taking IFNβ or GA. Elevated IL10 levels were associated with PHVI reactivation (p < 0.01). We revealed significant correlations between high levels of IL31 and VAE (p < 0.01), IL33 and PHVI (p < 0.01). The IL1β levels were significantly higher in individuals with PHVI reactivation treated with DMDs for MS. There were no differences in cytokine levels associated with the presence or absence of systemic AEs. The latter predominated in individuals with PHVI reactivation and VAE. The cytokine levels of individuals with MS are affected by treatment with DMDs for MS and herpesvirus infections.