Interleukin-6 inhibits the chemotaxis of human malignant plasma cell lines

The chemotaxis of human malignant plasma cells is promoted by two extracellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). We examined the effect of the supernatant from a bone marrow stroma cell line, KM-101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis-regulatory roles of the bone marrow microenvironment. Five human malignant plasma cell lines, FR4ds, OPM-1ds, U266/B1, RPMI-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM-1ds and U266/B1 cells showed chemotaxis promoted by FN (ChFN) and LN (ChLN). ARH-77 cells showed ChFN but not ChLN. RPMI-8226 cells did not show either ChFN or ChLN. The supernatant from KM-101 cells inhibited the chemotaxis of each of these cell lines regardless of whether the chemotaxis was promoted by FN or LN. Among the cytokines produced by KM-101 cells, it was postulated that IL-6 mediated this inhibitory effect because anti-IL-6 monoclonal antibody (MoAb) and anti-IL-6 receptor MoAb significantly reversed the inhibition. Recombinant IL-6 (rIL-6) also exhibited a similar inhibitory effect. Because anti-gp130 MoAb significantly reversed the chemotaxis inhibitory effect of rIL-6, the inhibitory signal is probably transduced via the signal transducing receptor component, gp130. The chemotaxis-regulatory effect is another previously unrecognized function of this pleiotropic cytokine, IL-6. High levels of IL-6 in the bone marrow microenvironment of patients with multiple myeloma appears to be favourable for the localization of myeloma cells there.