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.
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.
Single nucleotide polymorphisms in human pro- and anti-inflammatory genes, including IL1RN VNTR (rs315952), IL1A 4845G>T (rs17561), L1B-511C>T (rs16944), IL6-174G>C (rs1800795), IL10-1082 A>G (rs 1800896) and TNFα-308G>A (rs1800629) and their impact on multiple sclerosis risk and disease progression in a Polish population were investigated.
Considerable attention has been focused on studies evaluating disease-modifying effects in MS that identified seven genes of probable importance such as the HLA class II, ApoE, IL-1ra, IL-1β, TNF-α, TNF-β and CCR5 genes.
Together, our findings suggest that IL-1B and IL-1RN gene polymorphisms may not be relevant to the susceptibility to MS or the clinical characteristics of Greek MS patients.
With respect to MS, IL-1 beta (-511 C/T; rs16944), IL-1 beta (+3954 C/T; rs1143634), IL-1 alpha (-889 C/T; rs1800587), IL-1 alpha (+4845 G/T; rs17561), and the variable number of tandem repeats in intron 2 of the IL-1 receptor antagonist (IL-1RN) gene polymorphisms have been studied in different ethnic groups, leading to conflicting results.
Together, our findings suggest that IL-1beta or IL-1ra gene polymorphisms may not be relevant in the susceptibility to MS or the clinical characteristics of Japanese patients with 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.
Combining the available data on the IL1RN VNTR suggests that any effect of this gene on susceptibility to multiple sclerosis, or its progression is, at best, small.
This prolonged and quantitatively elevated induction of IL-1ra may contribute to the anti-inflammatory effect of IFNbeta and partially account for the reduction of exacerbation rate shown in most IFNbeta-treated MS patients.
The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.
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.