INTERACTION BETWEEN INTERLEUKIN-1 AND CILIARY NEUROTROPHIC FACTOR IN THE REGULATION OF NEUROBLASTOMA CELL FUNCTIONS

Human neuroblastoma cells SK-N-SH express significant numbers of IL-1R type I on their surface, as detected by saturation binding and RT-PCR , and are responsive to IL-1 beta activation by producing inflammatory cytokines IL-6 and IL-8, IL-1 beta can also have an indirect effect o n nervous cell functions, since it is able to modulate the stimulus-in duced increase of intracellular Ca++ levels, one of the first steps of the cell activation mechanism. In fact, on SK-N-SH neuroblastoma cell s, IL-1 beta can inhibit the Ca++ increase induced by stimulation of a cetylcholine receptors with carbachol. In parallel to IL-1 beta, the n eurotrophic factor CNTF also shows an inhibitory effect on carbachol-s timulated Ca++ increase in CNTFR alpha-expressing SK-N-SH cells, Howev er, when simultaneously present, the two cytokines cross-inhibit, thus allowing full cell activation in response to the cholinoceptor agonis t. The inhibitory effect of CNTF on IL-1 beta activities on nervous ce lls was confirmed in the IL-6 production assay. In fact, while CNTF co uld not induce IL-6 production, it could strongly inhibit cytokine pro duction in response to IL-1 beta in SK-N-SH cells. The down-modulation of IL-1 effects by CNTF could he one of the mechanisms controlling th e extent of the inflammatory reaction at the nervous system level.