IL-10 induces apoptosis in human monocytes involving the CD95 receptor/ligand pathway

The cytokine IL-10 exerts potent immunosuppressive and anti-inflammatory ef fects, although the mechanisms of this action remain largely unknown. In th e present study, we investigated the effects of IL-10 in human peripheral b lood monocytes. We were able to demonstrate that IL-10 dose- and time-depen dently triggers apoptosis in these cells as detected by annexin-V staining, the nick end labeling (TUNEL) procedure, electron microscopy and analysis of DNA laddering. IL-10-induced apoptosis required the activation of protea ses of the caspase family, since a peptide caspase inhibitor attenuated cel l death and, in addition, the proteolytic activation of caspase-8 was obser ved. Since caspase-8 has been implicated as a regulator of apoptosis mediat ed by death receptors, we investigated a potential involvement of the CD95 receptor/ligand system. Indeed, treatment of monocytes with IL-10 induced a dose-dependent up-regulation of CD95 receptor and ligand expression on the monocyte surface, Furthermore, a CD95 ligand-neutralizing antibody signifi cantly inhibited IL-10-induced apoptosis. In summary, our data show that IL -10 triggers monocyte apoptosis involving the CD95 system via an autocrine or paracrine process. Therefore, at least part of the anti-inflammatory pro perties of IL-10 may involve induction of apoptosis in monocytes.