INTERLEUKIN-1-BETA AND INTERFERON-GAMMA INTERACT WITH FIBROBLAST GROWTH FACTOR-II IN THE CONTROL OF NEUROBLASTOMA CELL-PROLIFERATION AND DIFFERENTIATION

Based on our previous observations that neuroblastoma (NB) cells expre ss fibroblast growth factor-2 (FGF-2; basic FGF) and respond to it [Ja net T. et al. (submitted); Wewetzer K. et al. (1993) J. Neurosci. Res. 36, 209-215), we attempted to find to what extent selected cytokines [interleukin (IL)-1 beta and interferon gamma (IFN gamma)] may modulat e FGF-mediated proliferative activity and differentiation. The NB cell lines IMR-32, SH-SY5Y, GIMEN and LAN-1 and colorimetric assays were u sed for the determination of cell numbers. IL-1 beta (and several othe r ILs, including IL-1 alpha, -2, -3, and 6) per se did not affect prol iferation of any cell line studied. IFN gamma inhibited growth of GIME N and LAN-1 cells, but was uneffective on IMR-32 and SH-SY5Y cells. FG F-2 was antimitogenic for GIMEN cells. IFN gamma reversed and IL-1 bet a enhanced this antimitogenic effect of FGF-2. FGF-2 per se did not af fect LAN-1 cells and did not modulate the growth inhibitory actions of IFN gamma on these cells. FGF-2 induced proliferation of IMR-32 and S H-SY5Y cells. This effect was not modulated by IFN gamma or IL-1 beta. These results suggest a heterogeneous response pattern of human NB ce ll lines towards the cytokines studied and complex interactions of FGF -2, IL-1 beta and IFN gamma.