Increased bioavailability of TNF-alpha in African Americans during in vitro infection: predisposing evidence for...

The objective of this study is to examine TNF-alpha and its soluble and membrane bound receptors in fetal membranes derived from blacks and whites in response to in vitro infectious stimulus, and the balance between TNF-alpha and the receptors. Fetal membranes collected from black and white women at term were maintained in an organ explant system and stimulated with lipopolysaccharide (LPS). TNF-alpha, soluble TNF receptors (sTNFR1 and sTNFR2) in culture media and membrane bound TNF receptors (TNFR1 and TNFR2) in tissue homogenates were measured. Molar ratio (TNF/sTNFR) was calculated between LPS stimulated and unstimulated (controls) cultures in both races. TNF-alpha was increased in both races after LPS stimulation and showed no difference between races (p=0.7). LPS decreased sTNFR1 in blacks, but increased in whites, showing a significant difference between races (p=0.001). In blacks sTNFR2 also decreased and increased in whites, but the results were not significant between races (p=0.4). Both TNFR1 and TNFR2 were increased in blacks after LPS stimulation whereas no such changes were seen in whites compared to controls that were also significant between races. After LPS stimulation TNF-alpha bioavailability was increased in blacks with a drop in soluble receptors and with an increase in membrane receptors. This was not evident in whites because in whites soluble receptors were increased with no change in membrane receptors. Our data demonstrated that LPS stimulation results in a molar ratio switch favoring TNF-alpha biofunction in blacks, but not in whites.