Cytokine-regulated secretion of nerve growth factor from cultured rat neonatal astrocytes

Interactions involved in the regulation of nerve growth factor (NGF) release by inflammatory cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) were examined in rat neonatal cortical astrocytes in primary culture. Exposure of cultured astrocytes to IL-1beta, IL-6, and TGF-beta1 resulted in the stimulation of NGF secretion. Treatment of cells for 24 h with IL-1beta (10 U/ml), IL-6 (5 ng/ml) and TGF-beta1 (5 ng/ml) caused 3-, 1.8-, and 2.8-fold increase in NGF secretion as compared to the control cells. In contrast, TNF-alpha (30 ng/ml) by itself had no stimulatory action on NGF release whereas co-stimulation of astrocytes with IL-1beta and TNF-alpha showed a synergistic interaction. Co-treatment of astrocytes with IL-1beta and TGF-beta1 increased NGF secretion in an additive way, whereas simultaneous application of IL-1beta and IL-6 resulted in the inhibitory effect on NGF secretion. Our results suggest that interactions between cytokines used cause the stimulation of NGF secretion through different regulatory mechanisms.