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, OPM4ds, U266/B1, RPM1-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM4ds, U255/B1, RPM1-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM4ds and U266/B1 cells showed chemotaxis promoted by FN (Ch(FN)) and LN (Ch(LN)). ARH-77 cells showed Ch(FN) or Ch(LN). RPMI-8226 cells did not show either Ch(FN) or Ch(LN). The supernatant from KM-101 cells inhibited the chemotaxis of each of these cell lines regardless of whether the chemotaxis was promoted by PN 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 m-h, the inhibitory signal is probably transduced via the signal transducing receptor component, gp130, The chemotaxis-regulatory effect is another previously unrecognized function of tills pleiotropic cytokine, IL-6. High levels of IL-6 in the bone marrow microenvironment of patients multiple myeloma appears to be favourable for localization of myeloma cells there.