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Mediators of Inflammation
Volume 12, Issue 2, Pages 89-94
http://dx.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

1Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, Amsterdam 1007 MB, The Netherlands
2Department of Cell Biology and Immunology, Vrije Universiteit Medical Centre, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands
3Department of Gastroenterology and Lab for Gastrointestinal Immunogenetics, Vrije Universiteit Medical Centre, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands
4Department of Epidemiology and Biostatistics, Vrije Universiteit Medical Centre, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands

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.

Abstract

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.