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We evaluated the effects of astrocyte\u2010targeted production of IL\u20106 in the CNS in the sterile\u2010nerve injury model of facial nerve axotomy. To accomplish this, facial nerve transection was performed in transgenic mice (glial fibrillary acidic protein [GFAP]\u2010IL6Tg) with IL\u20106 production under the GFAP promoter. Neuronal death, glial activation, lymphocyte recruitment, and integrin expression were evaluated by immunohistochemistry and flow cytometry from 3 to 28 days postinjury. Our findings revealed an increase in motor neuron cell death in GFAP\u2010IL6Tg mice correlating with changes in the microglial activation pattern, characterized principally by less attachment to neurons and reduced expression of both CD11b and CD18. We also found a higher CD4<jats:sup>+<\/jats:sup>T\u2010lymphocyte recruitment in GFAP\u2010IL6Tg mice. In addition, changes in the expression pattern of different integrins and their receptors were observed in transgenic animals. Specifically, alterations in osteopontin expression in motor neurons and its receptors CD44 and CD49e in lymphocytes and microglia, respectively, which may account for the variations related to glial reactivity and lymphocyte infiltration. In conclusion, our results indicated that forced local production of IL\u20106 has a direct impact on the outcome of nerve injury in the CNS inducing an increase in neurodegeneration, changes in glial response, and lymphocyte recruitment as well as in the expression of different integrins and their receptors. 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