POTENTIAL INDIRECT ANTIINFLAMMATORY EFFECTS OF IL-4 - STIMULATION OF HUMAN MONOCYTES, MACROPHAGES, AND ENDOTHELIAL-CELLS BY IL-4 INCREASES AMINOPEPTIDASE-N ACTIVITY (CD13 EC-3.4.11.2)

IL-4 up-regulates various monocytic properties that are associated wit h pro-inflammatory functions. Paradoxically, IL-4 may also act as an a nti-inflammatory agent by down-regulating the production of several in flammatory mediators. As the activity of some mediators has recently b een shown to be regulated by peptidases, we examined whether IL-4 was able to modulate the expression of a cell membrane-associated peptidas e, aminopeptidase-N (CD13). IL-4 caused a dose-dependent increase in t he expression of CD13 Ag on highly purified human blood monocytes. Max imal expression was observed around 48 h of culture. This IL-4-induced increase was completely blocked by anti-IL-4 antiserum. Furthermore, the increase in surface expression was preceded by increased mRNA leve ls of CD13, which was maximal around 24 h of culture. We also observed that CD13-mediated leucine-aminopeptidase activity of monocytes was i nduced by IL-4. Other CD13-expressing cells were also sensitive to IL- 4, as CD13 Ag expression and CD13 mRNA levels were up-regulated in hum an alveolar macrophages and endothelial cells upon IL-4 treatment. The increased expression of cell membrane aminopeptidase-N represents a p otentially increased cellular ability to inactivate inflammatory media tors. Therefore, these findings represent further evidence of IL-4-med iated anti-inflammatory actions. We postulate that up-regulation of am inopeptidase-N expression may be an indirect mechanism of IL-4 to modu late the action of bioactive peptides. This mechanism may underlie, at least partially, the anti-inflammatory effects of IL-4 in vivo.