The role of human herpesvirus-6 and inflammatory markers in the pathogenesis of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a destructive autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS) with unknown etiology and mechanism of pathogenesis. Pathogens, especially human herpes viruses, have been suggested as environmental factors of the MS and other neuroinflammatory disorders. This study aimed to determine the prevalence of HHV-6 antibody response in MS patients and investigate the levels of pro/anti-inflammatory cytokine and chemokines in MS patients in comparison with healthy subjects. Two hundred sixty-three patients with clinically defined MS (140 females and 123 males), along with 263 healthy subjects (140 females and 123 males), were recruited for this study. After the analysis of HHV-6 seropositivity/seronegativity, the levels of some pro/anti-inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, IL-6, and IL-12 as well as two chemokines, namely CCL-2 and CCL-5 were determined by the enzyme-linked immunosorbent assay (ELISA) method in HHV-6 seropositive/seronegative MS patients and healthy subjects. Our results showed that the serum concentrations of TNF-α, IFN-γ, IL-1β, IL-6, and CCL-5 elevated in HHV-6 seropositive compared with seronegative MS patients (P < .05). Moreover, the levels of IL-12, IL-10, and CCL-2 levels were significantly lower in seropositive MS patients when compared with seronegative MS patients (P < .05). Also, our results revealed that the mean values of the expanded disability status scale (EDSS) were significantly higher in HHV-6 seropositive versus seronegative MS patients (P < .05). In conclusion, we proposed that HHV-6 infection may play a role in MS pathogenesis by changing cytokine signaling in MS patients that may lead to peripheral inflammation.