Hans M. Schrijver, Jaco van As, J. Bart A. Crusius, Christien D. Dijkstra, Bernard M. J. Uitdehaag, "Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1β and IL-1ra production in multiple sclerosis", Mediators of Inflammation, vol. 12, Article ID 308935, 6 pages, 2003. https://doi.org/10.1080/0962933031000097691
Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1β and IL-1ra production in multiple sclerosis
Background: Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)- and IL-1 receptor antagonist genes (i.e. allele allele 2−) with disease severity in MS. Extending this observation, we investigated whether IL-1β and IL-1ra production differed depending on carriership of this gene combination.Methods: Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood, in vitro IL-1β and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide.Results: Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous for allele 2. In patients, Il-1ra production was higher and IL-1β production lower compared with controls. In primary progressive patients, the IL-1β /IL-1ra ratio was significantly lower than in relapsing-remitting patients.Conclusion: Our results suggest higher in vitro IL-1ra production in carriers of allele 2, with an indication of an allelic dose-effect relationship.
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