IL-4 inhibits H2O2 production and antileishmanial capacity of human cultured monocytes mediated by IFN-gamma.
The effect of IL-4 on the IFN-gamma-induced state of activation of cultured human monocytes was investigated with regard to their ability to produce hydrogen peroxide and their antileishmanial capacity towards the intracellular parasite Leishmania donovani. IL-4 was found to inhibit the IFN-gamma-dependent hydrogen peroxide production of monocytes. Treatment of monocytes with IFN-gamma (200 to 600 U/ml) for 48 h increased the hydrogen peroxide production fourfold above background. Coincubation of the monocytes with IL-4 (1 to 1000 U/ml) and IFN-gamma (200 to 600 U/ml) inhibited this increase by 50 to 100%. IL-4 alone did not modulate the hydrogen peroxide production of monocytes. Pretreatment of monocytes with IL-4 for 20 min to 3 h was already effective in preventing the IFN-gamma response. Addition of IL-4 not later than 6 h after the start of incubation with IFN-gamma was necessary for an optimal inhibitory effect. IL-4 also inhibited the IFN-gamma-induced antileishmanial capacity of monocytes: IFN-gamma (1000 U/ml) induced a 54 +/- 10% reduction in the number of parasites. Monocytes treated with combinations of IL-4 (100 to 1000 U/ml) and IFN-gamma (1000 U/ml) were unable to reduce the parasite numbers. IL-4 alone did not alter the uptake of Leishmania donovani nor induce antileishmanial activity. These results demonstrate that IL-4 disables human cultured monocytes to respond to IFN-gamma activation.
Lehn
M
M
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, MA 02115.
Weiser
W Y
WY
Engelhorn
S
S
Gillis
S
S
Remold
H G
HG
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D015847:Interleukin-4 / Q000494:pharmacology*; D007893:Leishmania donovani / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology*; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D006861:Hydrogen Peroxide