The induction by human interleukin-6 of apoptosis in the promonocytic cell line U937 and human neutrophils

Apoptosis of neutrophils at sites of inflammation in vivo is thought to lead to their recognition and safe elimination by macrophages. Little is known, however, about the regulation of apoptosis in myeloid cells. We report here that the human promonocytic leukemic cell line, U937, and mature human neutrophils can be induced to become apoptotic when cultured with interleukin-6. Apoptosis of U937 cells, assessed morphologically and by the presence of DNA fragmentation, was increased significantly in a dose-dependent fashion by concentrations of 0.5-100 ng/ml interleukin-6. Apoptosis of U937 cells was evident after 48 h of incubation with 20 ng/ml interleukin-6, and the effect was eliminated by adsorption of interleukin-6 with a specific monoclonal antibody. Apoptosis was not evident in the presence of the differentiating agent phorbol 12-myristate 13 acetate; the induction of apoptosis in U937 cells was not therefore a consequence of differentiation. Apoptosis of mature neutrophils was enhanced after 24 h in culture with interleukin-6. Interleukin-6 might be an important factor in the normal resolution of inflammation through the induction of apoptosis of neutrophils.