Interleukin-6 (IL-6) and cellular response to facial nerve injury: effectson lymphocyte recruitment, early microglial activation and axonal outgrowth in IL6-deficient mice

Nerve injury triggers numerous changes in the injured neurons and surroundi ng non-neuronal cells. Of particular interest are molecular signals that pl ay a role in the overall orchestration of this multifaceted cellular respon se. Here we investigated the function of interleukin-6 (IL6), a multifuncti onal neurotrophin and cytokine rapidly expressed in the injured nervous sys tem, using the facial axotomy model in IL6-deficient mice and wild-type con trols. Transgenic deletion of IL6 caused a massive decrease in the recruitm ent of CD3-positive T-lymphocytes and early microglial activation during th e first 4 days after injury in the axotomized facial nucleus. This was acco mpanied by a more moderate reduction in peripheral regeneration at day 4, l ymphocyte recruitment (day 14) and enhanced perikaryal sprouting (day 14). Motoneuron cell death, phagocytosis by microglial cells and recruitment of granulocytes and macrophages into injured peripheral nerve were not affecte d. In summary, IL6 lead to a variety of effects on the cellular response to neural trauma. However, the particularly strong actions on lymphocytes and microglia suggest that this cytokine plays a central role in the initiatio n of immune surveillance in the injured central nervous system.