Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Here we document for the first time that the cytokine IL-33 is upregulated in both the periphery and the CNS of MS patients. Plasma IL-33 was elevated in MS patients compared to normal subjects and a three-month treatment of MS patients with interferon β-1a resulted in significant decrease of IL-33 levels. Similarly, stimulated cultured lymphocytes and macrophages from MS patients had elevated IL-33 levels compared to normal subjects. In parallel, the transcription factor NF-κB that mediates IL-33 transcription was also elevated in leukocytes of MS patients. IL-33 was elevated in normal-appearing white matter and plaque areas from MS brains and astrocytes were identified as an important source of IL-33 expression in the CNS. In summary, IL-33 levels are elevated in the periphery and CNS of MS patients, implicating IL-33 in the pathogenesis of MS.

Interleukin-33 plasma levels in patients with relapsing-remitting multiple sclerosis

“…Previous studies have mentioned that IFN-β treatment could significantly suppress IL-33 plasma levels (56). In accordance with them, our assessments revealed that plasma levels of IL-33 in IFN-β-treated patients were significantly lower than in untreated patients (p < 001).…”

Targeting IL-33 in Autoimmunity and Inflammation

“…Brain inflammation may be evident in the earlier stages of the disease and may constitute a more reasonable target for drug development (Kozauer and Katz, 2013). Interestingly, IL-33 was also upregulated in astrocytes and peripheral leukocytes of MS patients (Christophi et al, 2012). Moreover, expression of IL-33 and IL-33 genes was increased in patients with remitting-relapsing MS (Zhang et al, 2014).…”

“…IL-33 has been implicated in MS (Christophi et al, 2012;Zhang et al, 2014). Luteolin has synergistic effect with IFN-b in inhibiting activation of peripheral blood mononuclear cells from MS patients (Sternberg et al, 2008(Sternberg et al, , 2009.…”

Photoimmunology and Multiple Sclerosis

“…We showed that UVB-induced IL-33 was involved in immune suppression because antibodies specific for IL-33 could block the effects of UVB exposure . MS patients have elevated levels of this cytokine within the CNS and periphery (Christophi et al 2012), suggesting IL-33 may play a pathogenic role during this disease. Resting mice also express IL-33 and its receptor (ST2) in the CNS, which is upregulated during EAE.…”