Interleukin-6 promotes post-traumatic healing in the central nervous system

The central nervous system (CNS) is an immune-privileged site where the rol e of immune cells and mediators in traumatic brain injury is poorly underst ood. Previously we have demonstrated that interleukin (IL)-6, a cytokine th at acts on a wide range of tissues: influencing cell growth and differentia tion, is an agonist for vascular endothelial growth factor (VEGF), in in vi tro vascularization assays for brain microvessel endothelial cells. In this present work we focus on the role of IL-6 in promoting tissue repair in th e CNS in vivo. An aseptic cerebral injury (ACI) was created in the right pa rietal cortex, using both wild type (C57B1/6J) and IL-6-deficient (C57B1/6J -IL-6-/-) mice to study the consequences of the absence of IL-6 on the path ology of brain injuries. We monitored the immediate, early, and late respon ses to this traumatic injury by characterizing several histologic features in the CNS at days 1, 4, 7 and 14 following injury. Acellular necrosis, cel lular infiltration, and re-vascularization were characterized in the injure d tissues, and each of these histologic features was individually graded an d totaled to assign a healing index. IL-B-deficient mice were found to have a comparatively slower rate of recovery and healing. Furthermore, fluoresc ein isothiocyanate (FITC)-dextran intravenous injection demonstrated leaky vessels in IL-6-deficient but not in wild type animals following ACI. Addit ionally, chronic expression of IL-6 in the CNS using transgenic GFAP-IL-6 m ice resulted in more rapid healing following ACI. The accelerated tissue re pair in GFAP-IL-6 transgenic animals is primarily due to extensive re-vascu larization as detected by endothelial cell markers. Combined, this data sug gests an important role of IL-6 in tissue repair processes following trauma tic injury in the CNS. (C) 2001 Published by Elsevier Science B.V.