Inhibitory cytokine circuits involving transforming growth factor-beta,
interferon-gamma, and interleukin-2 in human monocyte activation
I Espinoza-Delgado, MC Bosco, T Musso, K Mood, FW Ruscetti, DL Longo and L Varesio
Medicine Branch, National Cancer Institute, Bethesda, MD.
We have previously reported that transforming growth factor-beta 1 (TGF-
beta 1) inhibits interleukin-6 (IL-6) induction by IL-2 and IL-1 in fresh
human monocytes. We investigated the effects of TGF-beta 1 on the
expression of tumoricidal activity induced by IL-2 or interferon-gamma
(IFN-gamma) in human monocytes. We showed that TGF-beta 1 specifically
inhibited, in a dose-dependent manner, IL-2-induced but not IFN-gamma-
induced monocyte tumoricidal activity. The inhibitory effects of TGF- beta
1 on IL-2-activated monocytes were not caused by down-modulation of the
IL-2 receptor beta (IL-2R beta) because the treatment of monocytes with
IL-2 and TGF-beta 1 increased IL-2R beta mRNA expression. However, we found
that TGF-beta 1 down-modulated IL-2- induced IL-2R gamma mRNA, which may be
responsible for the TGF-beta 1 inhibition of monocyte activation by IL-2.
The resistance of the IFN- gamma-induced activation to the inhibitory
effects of TGF-beta 1 could be caused by the ability of IFN-gamma to
decrease TGF-beta 1 receptor expression, as shown by cross-linking
experiments. Overall, these results showed that TGF-beta 1 is a powerful
inhibitor of IL-2- but not of IFN-gamma-induced activation of monocytes to
a cytotoxic stage. This differential effect may be attributed to modulation
of cytokine receptor expression.
Volume 83,
Issue 11,
pp. 3332-3338,
06/01/1994
Copyright © 1994 by The American Society of Hematology
