Induction of soluble tumor necrosis factor receptor (sTNF-R75) release by HIV adsorption on cultured human monocytes

Soluble tumor necrosis factor (TNF) receptors were recently detected in the circulation of patients with early HIV-induced disease, at significantly higher levels than in control subjects. They were proposed as markers of disease progression and of the degree of immunodeficiency. We report that adsorption of heat-inactivated HIV-1 LAI to isolated human monocytes triggers the release of both TNF-alpha and its natural specific inhibitor, the soluble TNF receptor (sTNF-R)75, but not that of sTNF-R55. Only limited inhibition of sTNF-R release was obtained in the presence of a fully neutralizing anti-TNF-alpha monoclonal antibody, suggesting that stimulation by TNF-alpha was only partially responsible for sTNF-R release. HIV-1 LAI induced a higher sTNF-R/TNF ratio than lipopolysaccharide, a well-known monocyte activator. Monocytes thus represent a cellular source of sTNF-R that can be detected in the circulation of HIV-infected patients from seroconversion onwards. The release of sTNF-R could be of great significance in the control of HIV infection via the cytokine network and especially TNF-alpha.