Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells.
Single nucleotide polymorphisms (SNPs) in or near the <i>IL2RA</i> gene, that encodes the interleukin-2 (IL-2) receptor α (CD25), are associated with increased risk of immune-mediated diseases including multiple sclerosis (MS).
We further found that GA attenuates the LPS-triggered enhancement of IL-2, a highly produced cytokine in patients with active MS, in CD4<sup>+</sup> T cells co-cultured with glia, but not in CD4<sup>+</sup> T cells alone.
The goal of the article is to review the mechanism of action and the use of daclizumab, a humanized monoclonal antibody (mAb) against the alpha subunit of the high affinity interleukin-2 (IL-2) receptor, in the treatment of Multiple Sclerosis (MS).
Daclizumab is a humanized monoclonal antibody that binds to the α subunit (CD25) of the interleukin-2 receptor and favorably modulates the immune environment in multiple sclerosis (MS).
Carrying both the -330 T IL2 and the HLA, DRB1* 1501 alleles showed the most susceptibly effect to MS. Our data demonstrated -330 T IL2 allele provided major susceptibility to MS and HLA-DRB1* 1501 allele had an additive effect.
A central role for T cells in MS is supported by mouse models, association of the major histocompatibility complex region, and association of critical T cell growth regulator genes such as interleukin-2 receptor (IL-2RA) and interleukin-7 receptor (IL-7RA).
The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation.
These data strongly suggest that DAB(389)IL-2 specifically targeted myelin protein-activated CD4(+) T cells and strengthens the argument for the use of DAB(389)IL-2 in treatment strategies for MS.
For example, nucleotide variation in the interleukin 7 receptor (IL7RA), the interleukin 2 receptor (IL2RA), the CD58 and the c-type lectin domain family 16 member A (CLEC16A) genes has been consistently associated with MS in several populations.
In addition, IL2RA genetic variants correlate with the levels of a soluble form of the IL-2 receptor in subjects with type 1 diabetes and multiple sclerosis.
Variation in the genes encoding the interleukin (IL) 7 and IL2 receptor alpha chains (IL7RA, IL2RA) was recently found associated with multiple sclerosis (MS).
Here we use polychromatic flow cytometry to show that differences in surface expression of the human interleukin-2 (IL-2) receptor alpha (IL2RA, or CD25) protein are restricted to particular immune cell types and correlate with several haplotypes in the IL2RA region that have previously been associated with two autoimmune diseases, type 1 diabetes (T1D) and multiple sclerosis.
Together, our findings suggest that IL-2 gene polymorphisms do not influence the susceptibility to MS or the clinical characteristics of MS in Japanese patients.