Mediators of Inflammation

Mediators of Inflammation / 2003 / Article

Open Access

Volume 12 |Article ID 308935 |

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.

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)-1B and IL-1 receptor antagonist (IL1RN) genes (i.e. IL1RN allele 2+/IL1B+3959allele 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 IL1RN 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 IL1RN allele 2, with an indication of an allelic dose-effect relationship.

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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