Tumour necrosis factor (TNF) and TNF-related molecules in HIV-1+ individuals: relationship with in vitro Th1/Th2-type response.
We examined the secretion and expression by peripheral blood mononuclear cells (PBMC) of TNF-alpha 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-alpha/beta, interferon-gamma (IFN-gamma), 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-alpha and CD30 expression by flow cytometry. We found an expansion of the TNF system in HIV+ individuals, that positively correlated with TNF-alpha, IFN-gamma and sCD8, probably representing activation of the cytotoxic compartment. In advanced disease these correlations disappeared, and TNF-alpha 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-alpha are elevated.
Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
G P
GP
Rizzardi
J B
JB
Marriott
S
S
Cookson
A
A
Lazzarin
A G
AG
Dalgleish
W
W
Barcellini
D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D017730:Ki-1 Antigen; D014409:Tumor Necrosis Factor-alpha