Surface interleukin-10 inhibits listericidal activity by primary macrophages

Interleukin-10 (IL-10) down-regulates multiple functions of monocytes and m acrophages, including the ability of macrophages to kill many intracellular microorganisms. The experiments presented here test the hypothesis that IL -10 expressed on the cell surface inhibits the ability of primary mouse, ma crophages to kill the facultative, intracellular bacterium Listeria monocyt ogenes. We show that, in contrast to macrophages from normal mice, both bon e marrow-derived macrophages (BMDM) and thioglycollate-elicited macrophages obtained from IL-10(-/-) mice can kill L. monocytogenes. Treatment with an ti-IL-10 monoclonal antibody (mAb) enables BMDM from normal mice and thiogl ycollate-elicited macrophages from RAG-2(-/-) mice (which lack T or B cell- derived IL-10) to kill L. monocytogenes, and concurrently down-regulates th e expression of surface IL-10, Surface IL-10 on paraformaldehyde-fixed cell s can inhibit nitric oxide (NO) production by interferon-gamma (IFN-gamma)- stimulated macrophages from IL-10(-/-) mice, thus directly showing function al activity of surface IL-10. Taken together these studies indicate that ma crophage surface IL-10 is biologically active and down-regulates macrophage bactericidal activity.