INCREASED SERUM CONCENTRATIONS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTORS IN HIV-INFECTED INDIVIDUALS ARE ASSOCIATED WITH IMMUNE ACTIVATION

Serum concentrations of soluble tumor necrosis factor receptors (sTNF- Rs) were measured in 61 human immunodeficiency virus (HIV)infected ind ividuals. Thirty-five percent of these had increased serum concentrati ons of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrat ions of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4(+) T-cell count. However, the increase in co ncentrations of sTNF-R55 in the group with a CD4(+) T-cell count below the median was only moderate and did not reach statistical significan ce. A strong correlation was found between sTNF-R75 and the soluble im mune activation markers beta(2)-microglobulin (r(s) = 0.74, p<0.0001) and urinary neopterin (r(s) = 0.67, p<0.0001), and a less strong corre lation was found with interferon-gamma (r(s) = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were alwa ys weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4(+) T cells and sTNF-R75 (r(s) = -0.33, p = 0 .012), but no such correlation was observed with sTNF-R55. Our finding s suggest that increased concentrations of serum sTNF-Rs in HIV infect ion are linked to immune activation, in which synergistic actions of i nterferon-gamma and the TNF-alpha system are likely to play an importa nt role.