Immune cytokines and dexamethasone influence sensory regeneration in the avian vestibular periphery

Prior studies have shown that macrophages are recruited to sites of hair ce ll lesions in the avian inner ear in vitro (Warchol, 1997) and in vivo (Bha ve et al., 1998). Although the avian ear has a high capacity for sensory re generation (Oberholtzer & Corwin, 1997; Stone et al., 1998), the role of ma crophages in the regenerative process is uncertain. The present study exami ned the possible influence of macrophages and immune cytokines on regenerat ive proliferation in the avian utricle, one of the sensory endorgans of the vestibular system. Utricles from post-hatch chicks were placed in organ cu lture and hair cell lesions were created by incubation in neomycin. The cul tures were then maintained for an additional 24-48 hours in vitro, and some cultures were treated with dexamethasone, which inhibits macrophage activa tion and cytokine production. Following fixation, resident macrophages were identified by immunoreactivity to CD68. Labeled macrophages were present i n all specimens and increased numbers of macrophages were observed followin g neomycin treatment. Regenerative proliferation in dexamethasone-treated s pecimens was reduced by about 50%, relative to untreated controls. Addition al experiments showed that two macrophage secretory products-TGF-alpha and TNF-alpha-enhanced the proliferation of utricular supporting cells. The res ults are consistent with a role for macrophages in hair cell regeneration.