Di. Shin et al., Interleukin 10 inhibits TNF-alpha production in human monocytes independently of interleukin 12 and interleukin 1 beta, IMMUNOL INV, 28(2-3), 1999, pp. 165-175
Previously we demonstrated that endogenously produced Interleukin (IL-)10 s
uppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3
activated T-cells via downregulation of paracrine IL-12 secretion from APC.
Here we investigated the effect of endogenous IL-10 on TNF-alpha productio
n in purified lipopolysaccharide (LPS) stimulated monocytes and its mechani
sm. 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, IL12 and IL-1 bet
a, the neutralization of IL-12 or IL-1 beta did not affect the IL-10 effect
s on TNF-alpha production. This suggests that despite its inhibitory effect
s on IL12 and IL-1 beta, which is quite similarly observed in T-cells, in p
urified monocytes IL-10 does not effect its TNF-alpha suppression by this m
echanism. These findings indicate that IL-10 regulates production of pro-in
flammatory 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.