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Environmental factors and not genotype influence the plasma level of interleukin-1 receptor antagonist in normal individuals

Lookup NU author(s): Dr Hannah Cullup, Dr Peter Middleton, Professor Anne Dickinson


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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-1α and IL-1β, 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, IL1A 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.

Publication metadata

Author(s): Cullup H, Middleton PG, Duggan G, Conn JS, Dickinson AM

Publication type: Article

Publication status: Published

Journal: Clinical and Experimental Immunology

Year: 2004

Volume: 137

Issue: 2

Pages: 351-358

Print publication date: 01/08/2004

ISSN (print): 0009-9104

ISSN (electronic): 1365-2249

Publisher: Wiley-Blackwell


DOI: 10.1111/j.1365-2249.2004.02531.x

PubMed id: 15270852


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