Interleukin-1 beta and interferon gamma interact with fibroblast growth factor-2 in the control of neuroblastoma cell proliferation and differentiation.

Based on our previous observations that neuroblastoma (NB) cells express fibroblast growth factor-2 (FGF-2; basic FGF) and respond to it [Janet 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 modulate FGF-mediated proliferative activity and differentiation. The NB cell lines IMR-32, SH-SY5Y, GIMEN and LAN-1 and colorimetric assays were used for the determination of cell numbers. IL-1 beta (and several other ILs, including IL-1 alpha, -2, -3, and 6) per se did not affect proliferation of any cell line studied. IFN gamma inhibited growth of GIMEN and LAN-1 cells, but was uneffective on IMR-32 and SH-SY5Y cells. FGF-2 was antimitogenic for GIMEN cells. IFN gamma reversed and IL-1 beta enhanced this antimitogenic effect of FGF-2. FGF-2 per se did not affect 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 SH-SY5Y cells. This effect was not modulated by IFN gamma or IL-1 beta. These results suggest a heterogeneous response pattern of human NB cell lines towards the cytokines studied and complex interactions of FGF-2, IL-1 beta and IFN gamma.