1. ¹INSERM U 525, 30 rue Lionnois, 54000 Nancy, France
2. ²Centre de Médecine Préventive, 2, avenue du Doyen Jacques Parisot, 54500 Vandoeuvre-lès-Nancy, France

Correspondence: Dr S Visvikis, Unité INSERM 525, Faculte de Pharmacie, Centre du Médicament, Université Henri Poincaré Nancy 1, 30 rue Lionnois, Nancy, France. Tel: +33 3 8368 2184; Fax: +33 3 8332 1322; E-mail: Sophie.Visvikis@cmp.u-nancy.fr

Received 15 December 2003; Revised 10 August 2004; Accepted 19 August 2004; Published online 3 November 2004.

Abstract

Cytokines are involved in the development of several inflammatory diseases and atherosclerosis. Their variations in healthy individuals are not well defined. The aims of this study were: firstly, to identify factors affecting biological variation of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-); secondly, to study their family resemblance; and thirdly, to evaluate the effect of two TNF- (-308G/A and -238G/A) and two IL-6 polymorphisms (174G/C and -572G/C) on their corresponding circulating levels. A total of 171 healthy families selected from the STANISLAS cohort were studied. Age was negatively related to TNF- concentrations in offspring only (both sons and daughters). Additionally, IL-6 and TNF- levels were differently influenced by gender, white blood cells, tobacco consumption, and HDL-cholesterol level. A weak significant familial resemblance for TNF- concentration was observed in siblings only. There was no significant familial resemblance for IL-6 levels. The TNF- -308A allele was associated with decreased TNF- concentrations in both offspring aged less than 18 and males without overweight (BMI<25 kg/m²). Fathers carrying the IL-6 -174CC genotype had higher IL-6 levels than those with the IL-6 -174G allele. Parents with the IL-6 -572GG genotype had higher IL-6 concentrations than the C allele carriers. In this sample of healthy families, plasma levels of IL-6 and TNF- were differently affected by biological parameters including age, gender and smoking, and the impact of their respective polymorphisms was influenced by gender, age and BMI.