We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS).
In data-sets derived from the Finnish population we found no evidence for contribution of the T-cell receptor beta chain (TCR beta chromosome 7q35), immunoglobulin heavy chain (IGH chromosome 14q32), interferon-gamma (IFN-gamma chromosome 12q14-q15) or interleukin-1 receptor antagonist/interleukin-1 beta (IL-1ra/IL-1 beta chromosome 2q14-q21) loci in the genetic susceptibility to MS.
The data suggest that the IL-1 cluster genes make no major contribution to MS, but the tentative association between IL-1RA allele 2 and susceptibility of MS in women warrants further studies.
In addition, we observed no significant effect of the polymorphisms on brain or lesion volumes, Based on our data and those from the literature, one can conclude that there is currently no evidence to support a role for the IL-1 genes in MS.
Our findings support the existence of a causative variant for MS within this candidate region in a representative Italian Caucasian population and, in particular, the role of the IL-1 beta (-511 C/T) variant warrants further investigation.
Glatiramer acetate (GA), an immunomodulator used in multiple sclerosis (MS) therapy, induces the production of secreted IL-1 receptor antagonist (sIL-1Ra), a natural inhibitor of IL-1β, in human monocytes, and in turn enhances sIL-1Ra circulating levels in MS patients.
We investigated the association of specific polymorphisms of the interleukin IL-1b (AvaI -511 and TaqI +3,953) and IL-1 receptor antagonist (IL-1RN) (a variable number of tandem repeats; VNTR) genes with both the susceptibility to and the clinical characteristics in Greek multiple sclerosis (MS) patients cohort with bout-onset.
Moreover, IL-1 plays a significant role in the regulation of the T-cells, and it is considered an essential cytokine for the Th cell differentiation that implicated in the MS pathogenesis.
Common variants in the IL-1 region are not associated with MS risk but our data suggest that the IL-1ra VNTR polymorphism might be associated with bout-onset MS subtype.
The serum levels of numerous cytokines (IL-1β, IL-12, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-17) serum lipid levels, plasma insulin levels, and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels were evaluated in 123 female and 43 male patients with MS.
However, in an in vitro inflammasome activity assay with PBMC, IL-1β protein secretion and the IL-1β/IL-1Ra protein ratio were similar in MS patients and HC.
A significant association was found for the IL-1β +3953 T allele [OR=1.43, 95% CI (1.14-1.79), P value=0.002, Pc=0.01] and for IL-1β +3953 T/T genotype and MS risk [OR=1.92, 95% CI (1.25-2.96), P value=0.005, Pc=0.01].