Characterization of IL-4 receptor components expressed on monocytes and monocyte-derived macrophages: Variation associated with differential signaling by IL-4

The anti-inflammatory effects of IL-4 on activated monocytes differ from those on monocyte-derived macrophages (MDMac). While IL-4 suppresses LPS-induced IL-1beta, IL-12, IL-10 and TNFalpha production by monocytes, IL-4 suppresses only IL-1beta and IL-12 production by MDMac. The U937 and Mono Mac 6 cell lines have similar cytokine responses to IL-4 as monocytes and MDMac, respectively. The IL-4Ralpha and IL-2Rgamma (gammac) chains are well-characterized components of the IL-4 receptor. Cross-linking studies with I-125-IL-4 revealed that for monocytes and U937 cells. the binding of IL-4 to the receptor components was approximately 1:1 for IL-4Ralpha : gammac. In contrast, for MDMac and Mono Mac 6 cells that have a relative reduction in gammac surface expression, the binding of IL-4 to IL-4Ralpha : gammac was approximately 3:1. Furthermore, IL-4 induced IL-4Ralpha chain phosphorylation more rapidly in MDMac and Mono Mac 6 cells than in monocytes and U937 cells. This study identifies a correlation between altered I-125-IL-4 cross-linking to IL-4Ralpha : gammac, IL-4-induced signaling and regulation of pro-inflammatory cytokine production by IL-4.