Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid

Diffuse axonal injury is a frequent pathologic sequel of head trauma, which , despite its devastating consequences for the patients, remains to be full y elucidated. Here we studied the release of interleukin-6 (IL-6) into CSF and serum, as well as the expression of IL-6 messenger ribonucleic acid (mR NA) and protein in a weight drop model of axonal injury in the rat. The IL- 6 activity was elevated in CSF within 1 hour and peaked between 2 and 4 hou rs, reaching maximal values of 82,108 pg/mL, and returned to control values after 24 hours. In serum, the levels of IL-6 remained below increased CSF levels and did not exceed 393 pg/mL. In sial hybridization demonstrated aug mented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachno id spaces. A weak constitutive expression of IL-6 protein was shown by immu nohistochemical study in control brain. After injury, IL-6 increased at 1 h our and remained elevated through the first 24 hours, returning to normal a fterward. Most cells producing IL-6 were cortical, thalamic, and hippocampa l neurons as confirmed by staining for the neuronal marker NeuN. These resu lts extend our previous studies showing IL-6 production in the cerebrospina l fluid of patients with severe head trauma and demonstrate that neurons ar e the main source of IL-6 after experimental axonal injury.