INTERLEUKIN-6 PRODUCTION BY SCHWANN-CELLS AND INDUCTION IN SCIATIC-NERVE INJURY

Interleukin-6 (IL-6) was produced by the spontaneously immortal Schwan n cell clone, iSC, when cocultured with PC12 cells. The ISC cell-deriv ed IL-6 in co-culture conditioned media caused the neuronal differenti ation of naive PC12 cells and this bioactivity was neutralized by prei ncubation of conditioned media with antisera to IL-6. Cocultured ISC t ranscribe IL-6 message as confirmed by northern analysis. Stimuli that induce IL-6 production in the hematopoietic lineage induced transcrip tion and production of IL-6 by ISC cells. Lipopolysaccharide, tumor ne crosis factor-alpha, IL-1 alpha, IL-6, and serum withdrawal induced IS C cell IL-6 mRNA. The kinetics of IL-6 production was confirmed in the mouse IL-6-dependent B9 bioassay and that activity could be neutraliz ed with antisera to IL-6. Expression of both the IL-6 receptor and the gp130 signal transduction component by iSC as determined by northern analysis suggests an autocrine regulatory mechanism. The observed iSC production of IL-6 in vitro led to an investigation of the sciatic ner ve crush model of Schwann cell activation in vivo. In the initial 12 h after crush injury, IL-6 message is induced. IL-6 mRNA expression was highest distal to the crush injury. Our in vitro data demonstrate tha t iSC cells produce IL-6 in response to PC12 cell coculture and to sti muli that induce IL-6 production in the hematopoietic lineage. The ind uction of IL-6 message distal to a crush injury suggests another mecha nism by which Schwann cells facilitate peripheral nerve regeneration.