The proinflammatory cytokine interleukin-12 occurs as a cell membrane-bound form on macrophages

Phagocyte-derived interleukin-12 (IL-12) is a proinflammatory cytokine promoting cell-mediated immune responses in inflammatory and infectious disorders. Based on sequence homology of the p40 subunit with the interleukin-6 receptor it has been speculated that IL-12 could also exist as a membrane-bound form, but thus far only soluble (secreted) IL-12 has been identified. We have therefore analyzed human monocytic U937 and mouse P388D1 macrophages for membrane-bound IL-12 by flow cytometry. IL-12 is constitutively expressed on the cell surface of both cell lines. IL-12 cell surface staining is enhanced in response to stimulation with IFN-gamma plus LPS. IL-12 is also present in the supernatant of cultured P388D1 macrophages. Thus, in addition to a soluble form IL-12 occurs as a membrane-bound molecule on monocyte/macrophage cell lines.