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

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Abstract
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‐α 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‐α monoclonal antibody, suggesting that stimulation by TNF‐α 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‐α.