The IL-1 super-family of cytokines and receptors is highly pleiotropic and plays a fundamental role in the pathogenesis of several auto-inflammatory conditions including rheumatoid arthritis, multiple sclerosis and psoriasis.
We found that compared with placebo, probiotic supplementation down-regulated gene expression of interleukin-8 (IL-8; p < 0.001) and tumor necrosis factor-alpha (TNF-α) mRNA (p < .001) in peripheral blood mononuclear cells of patients with MS. We did not observe any significant effect of probiotic supplementation on gene expression of interleukin-1 (IL-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), or oxidized low-density lipoprotein receptor (LDLR) in peripheral blood mononuclear cells of patients with MS.
Interleukin-1 (IL-1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE).
Here, we review the recent findings showing an implication of the IL-1 system in EAE and MS, and introduce a model that highlights how IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) are interacting together to create a vicious feedback cycle of CNS inflammation that ultimately leads to myelin and neuronal damage.
This is consistent with the hypothesis that a lower propensity of macrophages to synthesise 25-HC will result in reduced negative feedback by 25-HC on IL-1 family cytokine production and exacerbated MS.
Due to the important roles that cytokines play as mediators in immune and inflammatory responses, we have evaluated the association of IL-1 gene cluster polymorphisms and haplotypes with MS susceptibility in 306 unrelated MS patients and 312 healthy matched controls.
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.
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.
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.
For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission.
This study investigates the association between IL-1 genes and MS by means of 70 markers spanning the 1.1 Mb region where the IL-1 genes map and exploring both the linkage disequilibrium (LD) and the haplotype structure in a case-control design including 410 subjects (160 patients and 250 controls).
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.
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.
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.
Differential expression of interleukins may influence susceptibility to inflammatory diseases such as MS. IL-1a production is increased in MS patients during acute relapse, IL-2 receptor (IL-2R) secretion correlates with disease activity in several inflammatory disorders and is variable in MS.
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).