Microglial cell-derived interleukin-6 influences behavior and inflammatory response in the brain following traumatic brain injury

Traumatic brain injury (TBI) is a major health problem with high rates of mortality and morbidity worldwide. The response of the brain to TBI is orchestrated by a number of cytokines, including interleukin-6 (IL-6). IL-6 is a major cytokine in the central nervous system and it is produced by different cells, such as neurons, glial cells, and endothelial cells. Since glial cells are one of the most important sources and targets of IL-6, we have examined the role of microglia-derived IL-6 in normal conditions and following a model of TBI, cryolesion of the somatosensorial cortex. To this end, tamoxifen-inducible microglial IL-6-deficient (Il6(Delta Mic), using Cx3cr1(CreER) model) mice and control (Il6(lox/lox)) mice were used. In normal conditions, microglial IL-6 deficiency reduced deambulation and exploratory behavior and decreased anxiety in a sex-dependent manner. The transcriptome profile following cryolesion was dramatically altered 1 day post-lesion in Il6(Delta Mic) compared with Il6(lox/lox) mice. However, the phenotype of Il6(Delta Mic) mice was less compromised in the following days, suggesting that compensatory mechanisms are at play.