INTERLEUKIN-6 RELEASED IN HUMAN CEREBROSPINAL-FLUID FOLLOWING TRAUMATIC BRAIN INJURY MAY TRIGGER NERVE GROWTH-FACTOR PRODUCTION IN ASTROCYTES

Cytokines are involved in nerve regeneration by modulating the synthes is of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigat ed by monitoring the release of IL-6 and NGF in ventricular cerebrospi nal fluid (CSF) of 22 patients with severe traumatic brain injuries. I L-6 was found in the CSF of all individuals and remained elevated for the whole study period. NGF appeared in the CSF if IL-6 levels reached high concentrations and was often detected simultaneously with or fol lowing an IL-6 peak. The amounts of NGF correlated with the severity o f the injury, as indicated by the clinical outcome of the patients. Th e functional relationship of IL-6 and NGF was investigated utilizing c ultured mouse astrocytes. The CSF of 8 patients containing IL-6 induce d NGF production in astrocytes, whereas control CSF without IL-6 had n o effect. The induction of NGF was inhibited up to 100% by adding anti -IL-6 antibodies. These results were corroborated when astrocytes were exposed to recombinant IL-6 at different concentrations resulting in NGF production. Thus, the production of IL-6 within the injured brain may likely contribute to the release of neurotrophic factors by astroc ytes.