ORIGINAL RESEARCH
First line therapy for multiple sclerosis: cytokine levels and the impact of herpesvirus infection
1 Yaroslavl State Medical University, Yaroslavl, Russia
2 Pirogov Russian National Research Medical University, Moscow, Russia
Correspondence should be addressed: Natalia S. Baranova
Revolutsionnaya, 5, Yaroslavl, 150000, Russia; ur.liam@sn_avonarab
Funding: the study was supported by the Foundation for Assistance to Small Innovative Enterprises in Science and Technology (Innovation Promotion Foundation) within the framework of the program UMNIK: Participant of the Youth Research and Innovation Contest (contracts No. 3560GU1/2014 dated 23.09.2014, No. 8815GU2/2015 dated 17.12.2015).
Author contribution: Baranova NS, Gris MS — study planning and design; Gris MS, Artyuhov AS — data acquisition and research procedure; Baranova NS, Gris MS, Baranov AA — data analysis; all authors — data interpretation; Baranova NS, Gris MS — manuscript drafting; all authors — manuscript editing.
Compliance with ethical standards: the study was approved by the local Ethics Committee of the Yaroslavl State Medical University (protocol No. 1 dated 10 October 2013). The informed consent was submitted by all patients.
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.
Keywords: cytokines, multiple sclerosis, adverse events, herpes, disease modifying drugs for multiple sclerosis