Chemokines and cytokines on the neuroimmunoaxis: Inner ear neurotrophic cytokines in development and disease. Prospects for repair?

The earliest stages of neuronal and sensory cell development in vertebrate sensory organs depend on "inflammatory" immune system neurotrophic cytokines/chemokines. Although classical nerve growth factors, brain-derived neurotrophic factors and glial growth factors play critical roles at various stages, the earliest directive roles belong to immune system cytokines. In frogs, fishes, birds and mammals, macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein 1 (MCP1) and RANTES, components of the otocyst-derived factor, are involved in sorting, morphogenesis, providing directional neuronal outgrowth cues as well as survival factors for both neurons and sensory cells. In this review we discuss their roles in the vertebrate inner ear.