F. Capsoni et al., IL-10 UP-REGULATES HUMAN MONOCYTE PHAGOCYTOSIS IN THE PRESENCE OF IL-4 AND IFN-GAMMA, Journal of leukocyte biology, 58(3), 1995, pp. 351-358
Interleukin-10 (IL-10), a cytokine produced by type 2 helper T (Th2) c
ells, inhibits the microbicidal effector function of interferon-gamma
(IFN-gamma)-activated macrophages. However, recent observations indica
te that IL-10 like IFN-gamma, increases Fc gamma RI expression and Fc
gamma R-mediated cytotoxic activity on human monocytes, suggesting tha
t this cytokine cannot be classified purely as a monocyte deactivator.
The present study found that incubation for 40 h of human monocytes o
r monocyte derived macro phages in the presence of IL-10 caused a sign
ificant enhancement of their capacity to ingest particles coated with
immunoglobulin G (Fc gamma R-mediated ingestion) or with C3b/C3bi frag
ments of the complement system (CR1/CR3-mediated ingestion). The numbe
r of phagocytosing cells (% phagocytosis) and the number of ingested p
articles per cell (phagocytic index) were both significantly higher af
ter 40-h incubation of monocytes with IL-10 concentrations greater tha
n or equal to 1 U/ml. This up regulating activity on phagocytosis was
completely reversed by anti-IL-10 monoclonal antibody (mAb), As previo
usly reported, IG 10 stimulated Fc gamma RI expression on monocytes bu
t did not induce the expression of Fc gamma RII, Fc gamma RIII, CR1, a
nd CR3, IFN-gamma, like IL-10, up-regulated only Fc gamma RI expressio
n but significantly reduced both Fc gamma R- and CR-mediated ingestion
, IL-10 almost completely reversed the IFN-gamma-induced inhibition of
both Fc gamma R- and CR-mediated phagocytosis, without concomitant ch
anges in membrane expression of phagocytic receptors. Exposure of mono
cytes to IL-4 reduced the membrane expression of all three Fc gamma Rs
and also inhibited Fc gamma R-mediated ingestion, On the other hand,
IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cul
tured monocytes, IL-10 not only neutralized the down-regulatory effect
of IL-4 on Fc gamma R expression but also completely reversed the IL-
4-induced suppression of Fc gamma R-mediated phap ocytosis. Fxpo sure
of monocytes to a combination of IL-10 and IL-4 resulted in a synergis
tic effect on CR-mediated ingestion, even though no additive effects w
ere observed on CR membrane expression, Finally, culture of monocytes
in medium containing anti-IL-10 mAb significantly reduced their capaci
ty to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for
endogenously produced II,10 in the modulation of phagocytosis by human
monocytes. These results demonstrate that IL-10 is a potent up-regula
tor of the phagocytic activity of human mononuclear phagocytes and ind
icate that this function may be in sensitive balance with the relative
concentrations of IL-10, IL-4, and IFN-gamma.