Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior

Interleukin-6 (IL-6) is a major cytokine which controls not only the immune system but also exhibits many other functions including effects in the central nervous system (CNS). IL-6 is known to be produced by different cells in the CNS, and all the major CNS do respond to IL-6, which makes it difficult to dissect the specific roles of each cell type when assessing the role of IL-6 in the brain. We have produced for the first time floxed mice for IL-6 and have crossed them with GFAP-Cre mice to delete IL-6 in astrocytes (Ast-IL-6 KO mice), and have compared their phenotype with that of mice with deletion of IL-6 receptor in astrocytes (Ast-IL6R KO mice). Our results indicate a major prosurvival role of the astrocyte IL-6 system at early ages (intrauterine life), which was also involved to various degrees in the control of adult body weight, locomotor activity, anxiety and exploratory behaviors. In some occasions deleting IL-6R in astrocytes mimicked the phenotype of Ast-IL-6 KO mice (i.e. activity), while in others the opposite was observed (i.e. exploration), suggesting autocrine and paracrine (presumably on neurons) roles of astrocyte IL-6. Our results suggest important roles of the astrocyte IL-6 system on normal brain physiology, in some cases totally unexpected from previous results with total IL-6 KO mice.