Differential responses of human monocytes and macrophages to IL-4 and IL-13.

The primary interleukin-4 (IL-4) recep- tor complex on monocytes (type I IL-4 receptor) includes the 140-kDa a chain (IL-4Ra) and the IL-2 receptor g chain, gc, which heterodimerize for intracellular signaling, resulting in suppression of lipopolysaccharide (LPS)-inducible inflamma- tory mediator production. The activity of IL-13 on human monocytes is very similar to that of IL-4 because the predominant signaling chain (IL-4Ra) is common to both receptors. In fact, IL-4Ra with IL-13Ra1 is designated both as an IL-13 receptor and the type II IL-4 receptor. When the anti- inflammatory activities of IL-4 and IL-13 were investigated on synovial fluid macrophages and compared with the responses by monocytes isolated from the patients at the same time as joint drainage, the response profiles differed with some responses similar in the two cell populations, others reduced on the inflammatory cells. Similar differences were recorded in the response profiles to IL-4 and IL-13 by monocytes and monocytes cultured for 7 days in macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF) (monocyte- derived macrophages, MDMac). MDMac have re- duced gc mRNA levels and reduced expression of the functional 64-kDa gc. There was a similar loss of IL-13Ra1 mRNA on monocyte differentiation. In turn, there was a significant reduction in the ability of IL-4 and IL-13 to activate STAT6. These findings suggest that different functional responses to IL-4 and IL-13 by human monocytes and macro- phages may result from reduced expression of gc and IL-13Ra1. J. Leukoc. Biol. 66: 575-578; 1999.