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

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 a 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.

► The first study documenting IL-33 expression in multiple sclerosis. ► IL-33 was elevated in plasma and activated leukocytes of MS patients. ► Three-month treatment with interferon β-1a suppressed plasma IL-33 levels. ► IL-33 was elevated in brains of MS patients and astrocytes highly expressed IL-33. ► IL-33 is elevated in the periphery and CNS, implicating IL-33 in MS pathogenesis.