Tumour necrosis factor production by IL-2-activated macrophages in vitro and in vivo.
Purified human and murine monocytes can be activated in vitro by human recombinant IL-2 to secrete tumour necrosis factor (TNF). TNF mRNA is detected within 4 h of addition of IL-2. Signal transduction does not appear to require expression of the Tac peptide of the IL-2 receptor. IL-2 does, however, induce Tac mRNA and Tac peptide expression on peripheral blood monocytes (PBM). In addition to these in vitro studies, PBM retrieved from IL-2-treated cancer patients and mice have been shown to have a greatly increased capacity for TNF production. These studies identify a pathway for macrophage activation by IL-2 both in vitro and in vivo. They also suggest a mechanism for some of the immunoregulatory and toxic effects of IL-2 based immunotherapy regimens.
Economou
J S
JS
John Wayne Cancer Clinic, UCLA School of Medicine 90024.
McBride
W H
WH
Essner
R
R
Rhoades
K
K
Golub
S
S
Holmes
E C
EC
Morton
D L
DL
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha