Open Access

ARTICLE

A three base pair gene variation within the distal 5’-flanking region of the interleukin-10 (IL-10) gene is related to the in vitro IL-10 production capacity of lipopolysaccharide-stimulated peripheral blood mononuclear cells

Horst Rieth¹, Maik Mörmann¹, Adriana J. F. Luty^1,2, Constance A. Assohou-Luty¹, Maria Roupelieva¹, Peter G. Kremsner^1,2, Dieter Kube^1,3

1 Sektion Humanparasitologie des Instituts für Tropenmedizin, Eberhard-Karls-Universität, Tübingen, Germany
2 Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
3 Georg-August-Universität Göttingen, Zentrum für Inner Medizin, Abteilung Hämatologie und Onkologie, Germany

* Corresponding Author: D. Kube,

European Cytokine Network 2004, 15(2), 153-158.

Accepted 16 April 2004;

Abstract

Interleukin-10 (IL-10) is an important multifunctional immunmodulator. There is evidence that IL-10 secretion is associated with certain genetic elements of the proximal IL-10 gene 5’-flanking region. The allelic and genotypic comparison of IL-10 expression by lipopolysaccharide (LPS)- stimulated leukocytes (PBMC) with a recently discovered distal “indel” DNA-sequence variation at – 7400 bp revealed significant inter-individual differences in the IL-10 in vitro production capacity. Homozygotes lacking the three base pairs “GGA” (– 7400del) at this gene locus are characterised by high expression of IL-10 with a median of 1690pg/ml (P ≤ 0.009). The allelic comparison supports this finding (P ≤ 0.002). Further analysis of the haplotype – 7400/– 1087 showed that homozygotes for – 7400del/– 1087G may be classified as very strong IL-10 responders with a median IL-10 secretion of 2378 pg/ml (P ≤ 0.025). When leukocytes were stimulated in vitro by dibutyryl-cAMP or infected with Epstein-Barr virus no significant inter-individual differences between the – 7400indel alleles or genotypes and the IL-10 in vitro production capacity were observed. Our findings further the understanding of the complexity of IL-10 gene regulation in relation to defined regulatory gene variations.

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