Environmental factors and not genotype influence the plasma level of interleukin-1 receptor antagonist in normal individuals.
Cytokine production may be regulated by both genotypic (single nucleotide or tandem repeat polymorphisms) and non-genotypic factors relating to the environment and inherent biology (i.e. gender). Interleukin (IL)-1 is one of the body's most highly proinflammatory cytokines and is implicated in the pathophysiology of numerous diseases, but also in the maintenance of homeostasis in a number of tissues. The cytokine IL-1 receptor antagonist (IL-1Ra) is the competitive inhibitor of the IL-1 agonists IL-1alpha and IL-1beta. In vivo IL-1Ra was measured in a cohort of 200 + blood donors and the effect of the IL-1 gene polymorphisms, environmental and biological factors assessed. In this study, we observed that possession of particular alleles of 5 IL-1 gene polymorphisms (IL1A-889, IL1Alpha VNTR, IL1B -511, IL1B +3953 and the IL1RN VNTR) did not correlate with higher plasma IL-1Ra levels. Environmental factors such as smoking and non-steroidal anti-inflammatory drug ingestion were associated with higher in vivo IL-1Ra levels (P = 0.015 and 0.022, respectively), but biological factors such as gender, age and menstruation status did not have any impact upon in vivo IL-1Ra levels. Genotypic associations of IL-1 gene family polymorphisms with disease features may reflect characteristics of stressed rather than normal control circuits for cytokine production.
Haematological Sciences, School of Clinical Laboratory Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. hannah.Cullup@ncl.ac.uk
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H
Cullup
P G
PG
Middleton
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G
Duggan
J S
JS
Conn
A M
AM
Dickinson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D012795:Sialoglycoproteins / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D012907:Smoking / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins