INTERLEUKIN-6 INHIBITS THE CHEMOTAXIS OF HUMAN-MALIGNANT PLASMA-CELL LINES

The chemotaxis of human malignant plasma cells is promoted by two extr acellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). W e examined the effect of the supernatant from a bone marrow stroma cel l line, KM-101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis-regulatory roles of the bone marrow microenv ironment. Five human malignant plasma cell lines. FR4ds, OPM4ds, U266/ B1, RPM1-8226 and ARH-77 showed different profiles of the expression o f beta 1 integrins of FN and LN receptors. FR4ds, OPM4ds, U255/B1, RPM 1-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM4ds and U266/B1 cells sh owed 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 pro moted by PN or LN. Among the cytokines produced by KM-101 cells, it wa s postulated that IL-6 mediated this inhibitory effect because anti-IL -6 monoclonal antibody (MoAb) and anti-IL-6 receptor MoAb significantl y reversed the inhibition. Recombinant IL-6 (rIL-6) also exhibited a s imilar inhibitory effect. Because anti-gp130 MoAb significantly revers ed the chemotaxis inhibitory effect of m-h, the inhibitory signal is p robably transduced via the signal transducing receptor component, gp13 0, 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.