1. ^*Division of Research, Department of Surgery, University Hospital, Zuerich, Switzerland
2. ^†Division of Trauma Surgery, Department of Surgery, University Hospital, Zuerich, Switzerland
3. ^‡Department of Neurosurgery, University Hospital, Zuerich, Switzerland
4. ^§Department of Biochemistry, Institute for Animal Anatomy and Physiology, University of Bonn, Bonn, Germany
5. ^¶Institute of Neuropathology, University Hospital, Bonn, Germany

Correspondence: Maria Cristina Morganti-Kossmann, Department of Surgery, Division of Research, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland.

Received 12 June 1997; Revised 8 May 1998; Accepted 11 May 1998.

Abstract

Diffuse axonal injury is a frequent pathologic sequel of head trauma, which, despite its devastating consequences for the patients, remains to be fully 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 (mRNA) 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 hours, 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 situ hybridization demonstrated augmented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachnoid spaces. A weak constitutive expression of IL-6 protein was shown by immunohistochemical study in control brain. After injury, IL-6 increased at 1 hour and remained elevated through the first 24 hours, returning to normal afterward. Most cells producing IL-6 were cortical, thalamic, and hippocampal neurons as confirmed by staining for the neuronal marker NeuN. These results extend our previous studies showing IL-6 production in the cerebrospinal fluid of patients with severe head trauma and demonstrate that neurons are the main source of IL-6 after experimental axonal injury.