Suppressive effect of PACAP 38 on myeloma cell growth and IL-6 release by bone marrow stromal cells. (A) Effect of PACAP on cell proliferation in human myeloma cells. Human κ-light chain–producing multiple myeloma cell line (NCI-929) was cultured in RPMI 1640 medium supplemented with 10% FBS and 0.05 mM 2-mercaptoethanol. The cell growth was determined by incorporation of BrdU during DNA synthesis. Myeloma cells grew approximately twice during 24 hours. Coculture of the cells with PACAP38 suppressed cell growth dose dependently with the maximum suppression with 10^–9 M. **P < .01 and *P < .05 compared with the control sample. (B) IL-6 secretion by human bone marrow stromal cells. The normal human bone marrow stromal cells produced low levels of IL-6. Addition of myeloma cells further increased expression of IL-6 by the BMSCs, reaching the maximum level during 24 hours of incubation. Myeloma cells alone do not secrete detectable levels of IL-6. (C) Addition of PACAP38 or dexamethasone suppressed myeloma cell–stimulated IL-6 secretion dose dependently, and maximum inhibition is seen at 10^–9 M, which inhibited IL-6 production by 90% to 95%. ***P < .001 and **P < .01 compared with the multiple myeloma plus an untreated sample of bone marrow stromal cells.