Regulation of tumor necrosis factor production in healthy humans and in patients with cancer.
To study the factors that influence cytokine release, the effect of endotoxin on in vitro tumor necrosis factor production by monocytes from debilitated patients with cancer (n = 6) was compared with that from healthy controls (n = 5). Spontaneous and endotoxin-stimulated monocyte tumor necrosis factor production was similar in patients with cancer and controls. However, with total peripheral blood mononuclear cells, enhancement of tumor necrosis factor production by endotoxin in patients with cancer (46 +/- 12, mean +/- SEM) was greater than in controls (0% +/- 7%). This enhanced response correlated with reduced peripheral blood mononuclear cell blastogenesis in response to phytohemagglutinin (r = .66) and could be partially reversed in vitro by addition of exogenous interleukin 2. Thus, a component of total peripheral blood mononuclear cells (probably T cells) seems to influence monocyte cytokine production in response to endotoxin. Moreover, this regulatory component is decreased in patients with cancer, correlates with decreased peripheral blood mononuclear cell blastogenesis, and can stimulated with interleukin 2.
Gough
D B
DB
University Department of Clinical Surgery, Royal Infirmary of Edinburgh, Scotland.
Winstanley
F P
FP
Fearon
K C
KC
Carter
D C
DC
D000328:Adult; D002448:Cell Adhesion; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology*; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004731:Endotoxins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli