Clinical significance of cytokine counting in patients with multiple sclerosis and its relationship with herpes infection

Baranova NS1, Gris MS1, Baranov AA1, Spirin NN1, Artyuhov AS2, Shakirova KM2, Nasonov EL3,4
About authors

1 Yaroslavl State Medical University, Yaroslavl, Russia

2 Pirogov Russian National Research Medical University, Moscow, Russia

3 Nasonova Research Institute of Rheumatology, Moscow, Russia

4 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

Correspondence should be addressed: Natalia S. Baranova
Revolutsionnaya, 5, Yaroslavl, 150000, Russia; ur.liam@sn_avonarab

About paper

Funding: the work was supported by the Innovations Assistance Fund within the framework of the UMNIK program: Participant of the youth scientific and innovative competition (contracts № 3560GU1/2014 of 23.09.2014, № 8815GU2/2015 of 17.12.2015).

Author contribution: NS Baranova, MC Gris — study planning and design, data analysis, manuscript authoring; MC Gris, AS Artyukhov, KM Shakirova — data collection and research; AA Baranov — data analysis; all autors — manuscript editing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Yaroslavl State Medical University (Minutes № 1 of October 1, 2013). All patients signed a voluntary informed consent.

Received: 2023-07-24 Accepted: 2023-08-20 Published online: 2023-08-31

There are persistent infections that contribute to the emergence and development of multiple sclerosis (MS) exacerbations; they are triggered by the Epstein–Barr, herpes type 6, herpes simplex types 1 and 2, varicella-zoster viruses. Cytokines are crucial to arresting the spread of a herpes infection in a body. If their production is out of balance, MS can progress faster. This study aimed at determining the level of cytokines in the blood serum of MS patients, assessing their clinical significance and how they affect reactivation of herpes infection. We examined 36 patients (12 male and 24 female) with confirmed MS (McDonald criteria) in remission. In 18 of them, we diagnosed reactivation of peripheral herpes virus. Serum levels of 15 cytokines (IL1ß, IL4, IL6, TNF-a, INF-γ, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, sCD40L) were determined with the help of xMAP multiplexing. Compared to the control group, MS patients had increased levels of IL10, IL33 (p < 0.001), with high IL33 identified most often (20 patients; 52.8%). During exacerbations, the average level of IL10 grew up (p < 0.01), as did that of IL31, the high levels of which were detected significantly more often (42.8 and 6.9%, respectively; p = 0.04). In addition, a prevailing scenario was the increased levels of IL33 and other cytokines (IL17A, IL17F, IL21, IL31) (57.1 and 6.9% of cases, respectively; p = 0.008). Reactivation of herpes translated into higher levels of IL1ß, IL23 and IL33 compared to cases without reactivation (p < 0.05 and p < 0.01, respectively). High levels of IL33 were significantly more frequently recorded in this group of patients (77.7 and 33.3%; p = 0.008). We discuss involvement of IL10, IL31, IL33 and other cytokines in the pathogenesis of herpes-associated MS.

Keywords: cytokines, multiple sclerosis, herpes, interleukin 10, interleukin 31, interleukin 33