Identification of interleukin-6 as a factor that induces neurite outgrowth by PC12 cells primed with NGF.

We have screened for a factor that induces neurite outgrowth by PC12 cells only after NGF pretreatment in the supernatants of 38 transformed cell lines, finding three positive clones. The factor showing the strongest activity was purified and identified as IL6. In this NGF-IL6 system, the process of neurite outgrowth by PC12 cells can be separated into NGF-dependent and IL6-dependent steps. The IL6-dependent step requires RNA synthesis, suggesting that IL6 induces new gene expression depending on NGF-priming. These findings suggest that the gene expression during the differentiation process is regulated by at least two signals.