Interleukin-1 induces tumor necrosis factor (TNF) in human peripheral blood mononuclear cells in vitro and a circulating TNF-like activity in rabbits.
Recombinant human interleukin-1 (IL-1), injected into rabbits, induces the synthesis of endogenous IL-1. Also, IL-1 induces its own gene expression and synthesis in human peripheral blood mononuclear cells (PBMC). In this study, tumor necrosis factor-alpha (TNF-alpha) production by PBMC of 40 individuals stimulated with IL-1 alpha or IL-1 beta was determined by specific radioimmunoassay (RIA). After 3 h of PBMC incubation with IL-1, TNF-alpha mRNA was detected. IL-1 alpha stimulated both IL-1 beta and TNF-alpha, but there was no correlation in the amount of TNF-alpha or IL-1 beta synthesized in the PBMC of 29 individuals. IL-1-stimulated adherent cells produced approximately 50% more TNF-alpha than did unfractionated PBMC. Coincubation with interferon-gamma (IFN-gamma) did not change the amount of IL-1-induced TNF-alpha, whereas in the same culture IFN-gamma inhibited (greater than 70%) IL-1-induced IL-1 production. Endogenous pyrogen and TNF-like activity were detected in the sera of rabbits 3.5 h after injection of either IL-1 alpha or -1 beta. These studies demonstrate that IL-1 induced TNF-alpha production in vivo and in vitro.
Ikejima
T
T
Department of Medicine, New England Medical Center Hospital, Boston, MA 02111.
Okusawa
S
S
Ghezzi
P
P
van der Meer
J W
JW
Dinarello
C A
CA
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011863:Radioimmunoassay; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma