Increased serum level of IL-37 in patients with multiple sclerosis and neuromyelitis optica

Abstract

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.

Plasma levels and expression of interleukin‑37 in patients with immune thrombocytopenia

“…IL-37, a novel member of the IL-1 family, has been recognized as an important anti-inflammatory cytokine expressed by immune cells. Abnormal expression of IL-37 has been reported in various autoimmune diseases, including SLE, RA, IBD, GD and AS (18)(19)(20)(21)(22)(23)(24)(25)(26)(27), as a potential negative factor influencing the development of these disorders. According to Ye et al (22), increased IL-37 expression was associated with SLE disease activity, and IL-37 levels were significantly higher in patients with renal disease.…”

“…Aberrant expression of IL-37 has been observed in several inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) (18)(19)(20)(21), systemic lupus erythematosus (SLE) (22,23), inflammatory bowel disease (IBD) (24,25), ankylosing spondylitis (AS) (26) and Graves' disease (GD) (27). However, the role of IL-37 in ITP has remained elusive.…”

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

“…Aberrant expression of IL-37 has been reported in autoimmune diseases, such systemic lupus erythematosus (40), rheumatoid arthritis (41), inflammatory bowel disease (42), and psoriasis (43); however, its role in MS has not yet been documented. Only a recent paper demonstrated an increased serum level of IL-37 in patients with MS, which suggests that this cytokine is a part of a feedback loop to control the underlying inflammation in MS pathogenesis (44). IL-37 generally acts via an intracellular mechanism that translocates to the nucleus (22, 45, 46).…”

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

“…Farrokhi et al showed that IL37 serum levels were higher both in patients suffering from relapsing-remitting MS (RR-MS) and those with neuromyelitis optica (NMO) as compared to healthy controls. In addition, they noticed a positive correlation between the serum levels of IL37 and Expanded Disability Status Scale (EDSS) of patients [33]. These findings were subsequently confirmed in another independent study that demonstrated that serum levels of IL37 were higher in patients with MS and correlated with disease activity as well as with the levels of IL33 and soluble vascular endothelial growth factor (VEGF) receptor 2 [34].…”

“…In spite of these data of IL37 in autoimmune diseases, only a limited number of studies have evaluated the possible role of this cytokine in MS [33][34][35][36]. Farrokhi et al showed that IL37 serum levels were higher both in patients suffering from relapsing-remitting MS (RR-MS) and those with neuromyelitis optica (NMO) as compared to healthy controls.…”