The gp 130 family cytokines IL‐6, LIF and OSM but not IL‐11 can reverse the anti‐proliferative effect of dexamethasone on human myeloma cells

In order to understand the mechanisms supporting steroid escape in patients with multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2 and L363, have been treated with dexamethasone in the presence or absence of cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11. With pharmacological doses of dexamethasone, a dramatic growth arrest was observed in all the cell lines. IL-6 completely reversed this inhibition. Of note, this IL-6 induced reversion was still seen with very low amounts of IL-6 (12 pg/ml). Finally, whereas LIF and OSM had clear growth-promoting effects on OPM2 only, both cytokines (but not IL-11) reversed the dexamethasone-induced growth arrest in all the cell lines. Therefore the high levels of IL-6 (ng/ml) observed in the MM intermediate milieu and the putative presence of LIF and OSM can easily counteract the effects of dexamethasone in vivo.