Tumor necrosis factor alpha and soluble tumor necrosis factor receptors in individuals with human immunodeficiency virus infection

Abstract

There is some ongoing debate as to whether tumor necrosis factor (TNF) alpha levels are elevated in human immunodeficiency virus infection (HIV), however TNF alpha is rapidly cleared from the circulation and long-term markers have to be analyzed. Two distinct TNF alpha receptors have been identified, which also exist in soluble forms. The aim of this study was to investigate whether an association in HIV infection exists between the serum levels of TNF alpha, the two soluble TNF receptors (sTNFRs) and other soluble immune activation markers, namely neopterin and β2-microglobulin, and the number of CD4 + T-cells. We investigated 63 individuals with HIV infection for serum levels of TNF alpha, sTNFR 55, sTNFR 75, β2-microglobulin and urinary neopterin. The study population comprised all stages of HIV infection: 35 were asymptomatic, 8 had oral candidiasis, 4 had constitutional signs and 16 had AIDS. Circulating levels of TNF alpha were detectable in 22 of 63 (34.9%) individuals. For those with detectable TNF alpha levels the median concentration was 40 pg/ml. The frequency and extent of TNF alpha levels found in those with advanced HIV infection as defined by a CD4 + T-cell count below 320 × 10 6/l did not differ significantly compared to those with a higher CD4 + T-cell count. Increased concentrations were found in 69.8% of the patients for sTNFR 55 and in 87.3% for sTNFR 75. Serum concentrations of sTNFR 55 and sTNFR 75 were higher in the group with the lower CD4 T-cell count ( P = 0.006 and P = 0.0003). TNF alpha correlated with sTNFR 75 and weakly with sTNFR 55 and β2-microglobulin. The correlation found between sTNFR 75 and urinary neopterin (r s = 0.52, P < 0.0001) and β2-microglobulin (r s = 0.52, P < 0.0001) was stronger than that with TNF alpha (r s = 0.45, P = 0.0004). The findings suggest that shedding of sTNFRs are linked to immune activation where synergistic actions of interferon gamma and the TNF alpha system are likely to play an important role.