Inhibition of macrophage inflammatory protein-1α expression by IL-10 - Differential sensitivities in human blood monocytes and alveolar macrophages

IL-10 is a pleiotropic cytokine produced by monocytes and T cells that has potent inhibitory effects on monocyte/macrophage function. Because monocytes and macrophages are capable of releasing the C-C chemokine, macrophage inflammatory protein-1α (MIP-1α), which is a potent chemoattractant for activated T cells, we studied the effects of IL-10 on the expression of MIP-1α in these cells. Low levels of MIP-1α were detectable in resting monocytes and macrophages. Both LPS (1 μg/ml) and IL-1β (10 μg/ml) induced the expression of MIP-1α mRNA and the release of MIP-1α protein from these cells. The addition of exogenous human rIL-10 inhibited induced MIP-1α mRNA expression as well as the release of MIP-1α protein measured after 24 h. This inhibition was significantly higher in monocytes compared with alveolar macrophages. In monocytes, IL-10-induced inhibition of MIP-1α was only partially accounted for by alterations in mRNA stability and was dependent on de novo protein synthesis. In the presence of an anti-human IL-10-neutralizing Ab, the release of MIP-1 a induced by LPS and IL-10 was further enhanced in monocytes but unchanged in alveolar macrophages. MIP-1α mRNA was also increased in monocytes. There was no detectable release of IL-10 from alveolar macrophages after LPS or IL-1β in contrast to modest amounts released from monocytes. Thus, IL-10 is an inhibitor of the induced transcription of MIP-1α mRNA and of the release of MIP-1α protein, with a greater effect on monocytes as compared with alveolar macrophages. IL-10 may indirectly regulate effects on cells such as activated T lymphocytes partly through the inhibition of MIP-1α expression from monocytes and macrophages.