Multiple sclerosis (MS) is a common autoimmune disease of central nervous system in which neurodegenerative and inflammatory mechanisms cause alternate neurological impairments. Many inflammatory and anti-inflammatory cytokines were suggested as contributor in MS pathogenesis, and the balance between these opposing cytokines can regulate MS severity. IL-37, an anti-inflammatory cytokine, is the most recently identified member of IL-1 family, which acts as a natural inhibitor of innate immunity. However, the role of IL-37 in MS has not investigated so far. Therefore, in this study, we aimed to measure serum level of IL-37 in patients with relapsing remitting multiple sclerosis (RRMS) and neuromyelitis optica (NMO). In a case-control study, plasma was collected from healthy controls (n = 49) and also patients with RRMS (n = 122) and NMO (n = 31). Serum level measurement of IL-37 was performed using enzyme-linked immunoassay (ELISA) method. The serum levels of IL-37 were 247.46 ± 74.02 and 312.00 ± 86.72 and 114.63 ± 20.58 in RRMS and NMO patients and healthy controls, respectively, showing statistically significant difference between them (P = 0.00). Furthermore, we found a positive correlation between the serum levels of IL-37 and EDSS of patients (r = +0.31 and P = 0.00). In summary, the serum level of IL-37 was found to be significantly increased in MS patients compared to healthy controls. Furthermore, the mean serum level of IL-37 was correlated with disease severity. This suggests that IL-37 may be part of a feed-back loop to control underlying inflammation in MS pathogenesis. However, further studies will be required to indicate exact role of IL-37 in the MS pathomechanisms.

In summary, the present study provides the first evidence that the rs11556218T/G and rs4072111C/T polymorphisms of IL-16 gene were significantly associated with increased risk of MS. These results suggest that rs11556218T/G, rs4072111C/T, and rs4778889T/C polymorphisms of IL-16 may contribute to susceptibility to MS through increased expression of IL-16 levels.

Taken together, we cannot definitely conclude that TNF-α does not play an important role in pathogenesis of MS. However, other characteristics of monocyte activation such as IL-6 or TLRs can elucidate implication of peripheral blood monocytes in MS pathogenesis.

In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression. Furthermore, our study provides preliminary evidence for the activation of innate immunity in the pathogenesis of MS. In addition, the findings of the present study suggest serum level of sCD14 as candidate biomarker of MS severity.

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