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

Abstract

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.