The influence of interleukin-1 receptor antagonist transgene on spiral ganglion neurons.
The cytokine interleukin-1beta (IL-1) has been shown to induce the secretion of NGF and GDNF in several types of neuronal populations. IL-1 has also been shown to mediate immune response following trauma or presence of foreign antigens. We investigated the influence of an IL-1 antagonist on the survival of spiral ganglion neurons in inner ears in which hair cells have been eliminated. We used a replication-deficient adenoviral vector containing the human IL-1 receptor antagonist (IL-1ra) cDNA. Guinea pigs were bilaterally deafened with ototoxic drugs. One week later their left cochleae were inoculated with the IL-1ra vector, designated Ad.IL-1ra. The vector was delivered by injection through the cochlear round window. IL-1ra protein levels within the perilymph of Ad.IL-1ra-injected animals were measured with ELISA and found to be significantly elevated compared to our controls. Spiral ganglion cell counts in experimental ears revealed a lower density of neurons after Ad.IL-1ra inoculation. Taken together, the data suggest that the Ad.IL-1ra-infected cochlear cells synthesized the transgenic human IL-1ra protein, which was then secreted by the cells into the perilymph, resulting in an accelerated neuronal degeneration in hair cell-depleted ears.
Komeda
M
M
Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor 48109-0680, USA.
Roessler
B J
BJ
Raphael
Y
Y
D000818:Animals; D002452:Cell Count; D003051:Cochlea / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D006168:Guinea Pigs; D006651:Histocytochemistry; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007763:Lac Operon / Q000235:genetics; D008297:Male; D009474:Neurons / Q000502:physiology; D010590:Phalloidine; D012795:Sialoglycoproteins / Q000235:genetics*; D013136:Spiral Ganglion / Q000166:cytology / Q000502:physiology*; D019076:Transgenes / Q000502:physiology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D010590:Phalloidine