Tumour necrosis factor (TNF) and TNF‐related molecules in HIV‐1+ individuals: relationship with in vitro Thl/Th2‐type response
We examined the secretion and expression by peripheral blood mononuclear cells (PBMC) of TNF‐α and TNF‐related molecules with regard to Th1/Th2‐type cytokine production. In 76 HIV+ patients at different disease stages and in 25 controls we measured cytokine (TNF‐α/β, interferon‐gamma (IFN‐γ), IL‐2, IL‐4, IL‐10), and activation marker secretion (sCD4, sCD8, sCD30) in phytohaemagglutinin (PHA)‐stimulated and unstimulated PBMC cultures by ELISA, and membrane‐bound TNF‐α and CD30 expression by flow cytometry. We found an expansion of the TNF system in HIV+ individuals, that positively correlated with TNF‐α, IFN‐γ and sCD8, probably representing activation of the cytotoxic compartment. In advanced disease these correlations disappeared, and TNF‐α and TNF‐related molecules positively correlated with IL‐10. Our results are in line with the hypothesis that an expanded TNF system is immunopathological in conjunction with Th2‐type immunity in the advanced stage of disease and with the inexorable progression to disease seen when both IL‐10 and TNF‐α are elevated.