Interleukin 10 inhibits TNF-alpha production in human monocytes independently of interleukin 12 and interleukin 1 beta.
Previously we demonstrated that endogenously produced Interleukin (IL-)10 suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via down-regulation of paracrine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, IL-10 inhibited monocyte TNF-alpha production by about half. Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the IL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.
Shin
D I
DI
Department of Pediatric Hematology and Oncology, Heinrich-Heine-University Medical Center Düsseldorf, Germany.
Banning
U
U
Kim
Y M
YM
Verheyen
J
J
Hannen
M
M
Bönig
H
H
Körholz
D
D
D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12