Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1beta 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 (IL-1RN) genes (i.e. IL-1RN allele 2+/IL-1B(+3959)allele 2-) with disease severity in MS. Extending this observation, we investigated whether IL-1beta 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-1beta 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 IL-1RN allele 2. In patients, Il-1ra production was higher and IL-1beta production lower compared with controls. In primary progressive patients, the IL-1beta /IL-1ra ratio was significantly lower than in relapsing-remitting patients.


CONCLUSIONS
Our results suggest higher in vitro IL-1ra production in carriers of IL-1RN allele 2, with an indication of an allelic dose-effect relationship.
Schrijver
Hans M
HM
Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. HM.Schrijver@vumc.nl
van As
Jaco
J
Crusius
J Bart A
JB
Dijkstra
Christien D
CD
Uitdehaag
Bernard M J
BM
D000328:Adult; D000483:Alleles; D005260:Female; D018628:Gene Dosage; D006579:Heterozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins