Effects of human immunodeficiency virus and colony-stimulating factors on the production of interleukin 6 and tumor necrosis factor alpha by monocyte/macrophages.
Patients infected with human immunodeficiency virus (HIV) frequently have increased production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and these cytokines may in turn contribute to the disease pathogenesis. It has been hypothesized that secretion of these cytokines by HIV-exposed mononuclear cells or HIV-infected monocyte/macrophages (M/Ms) is the principal source of their overproduction in HIV-infected patients, and the present study was undertaken to explore this issue. We observed that in the absence of endotoxin or cytokines, M/Ms productively infected by HIV do not produce detectable IL-6 or TNF-alpha. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances HIV replication in M/Ms and is frequently used to propagate monocytotropic strains of HIV, can induce the relatively long-term production of IL-6 (up to 47 U/ml) and TNF-alpha (up to 47 pg/ml) by M/Ms, even in the absence of HIV. Also, HIV induced production of a relatively small (< or = 9 U/ml) quantity of IL-6 in M/Ms stimulated with macrophage-colony stimulating factor (M-CSF). Finally, while highly concentrated HIV induced production of both cytokines by either M/Ms or peripheral blood mononuclear cells (PBMCs), this production was almost completely eliminated when care was taken to avoid contamination of HIV by endotoxin. These data suggest that the excess IL-6 and TNF-alpha in HIV-infected patients does not simply result from their production by HIV-infected M/Ms and that alternative mechanisms are involved in this process.
Foli
A
A
HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Saville
M W
MW
May
L T
LT
Webb
D S
DS
Yarchoan
R
R
D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000302:isolation & purification / Q000633:toxicity; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015658:HIV Infections / Q000209:etiology / Q000276:immunology; D015497:HIV-1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D003115:Colony-Stimulating Factors; D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor