TUMOR-NECROSIS-FACTOR (TNF) GENE POLYMORPHISM INFLUENCES TNF-ALPHA PRODUCTION IN LIPOPOLYSACCHARIDE (LPS)-STIMULATED WHOLE-BLOOD CELL-CULTURE IN HEALTHY HUMANS

TNF-alpha is involved in infectious and immune-inflammatory diseases. Different individuals may have different capacities for TNF-alpha prod uction. This might determine a predisposition to develop some complica tions or phenotypes of these diseases. The aims of our study were to a ssess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-a lpha production after LPS stimulation was evaluated using a whole bloo d cell culture model. The TNF gene polymorphism was studied by an alle le-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successful ly genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozy gotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNF1 homozygotes (92 9 pg/ml (480-1473 pg/ml) versus 521 pg/ml (178-1307 pg/ml); P < 0.05). This difference was even more significant after correction of TNF-alp ha production for CD14 expression on blood cells. In conclusion, the s ingle base pair polymorphism at position -308 in the TNF gene may infl uence TNF-alpha production in healthy individuals.