Contrasting effects of IL-4, IL-10 and corticosteroids on RANTES production by human monocytes

RANTES is a chemokine produced in delayed-type hypersensitivity(DTH) and allergic reactions, in which it may contribute tothe recruitment of immune cells. Macrophages participate inthe cellular infiltration in both conditions and they representa potent source of RANTES. To understand the regulation of RANTESproduction by human monocytes, we analyzed the effect of cytokinesand of corticosteroids on this production. We showed that IFN-and tumor necrosis factor (TNF)- cooperated to induce RANTESproduction by monocytes. N-acetylcysteine inhibited this effect,indicating that reactive oxygen intermediates are required forRANTES production. Both IL-10 and corticosteroids antagonizedthe stimulating effect of IFN- and TNF- on RANTES production.In contrast, IL-4 had no effect on IFN--induced RANTES productionand it potentiated the positive effect of TNF- on this production.Thus, the deactivating properties of IL-10 and corticosteroidson macrophage functions include RANTES production, and thismay contribute to the immuno-suppressive effect of both compoundsin DTH and allergic reactions. In contrast, IL-4 has an oppositeeffect on RANTES production and this property may contributeto cell recruitment in allergic reactions. Therefore, althoughIL-10 and IL-4 belong to the T_h2 family of cytokines, they candisplay distinct functions in immune reactions.