Delivery of Interleukin‐4–Encoding Lentivirus Using Multiple‐Channel Bridges Enhances Nerve Regeneration

Abstract

Objectives/Hypothesis: Facial nerve injury is a source of major morbidity. This study investigated the neuroregenerative effects of inducing an anti-inflammatory environment when reconstructing a facial nerve defect with a multichannel bridge containing interleukin-4 (IL-4)-encoding lentivirus. Study Design: Animal study. Methods: Eighteen adult Sprague-Dawley rats were divided into three groups, all of which sustained a facial nerve gap defect. Group I had reconstruction performed via an IL-4 multichannel bridge, group II had a multichannel bridge with saline placed, and group III had no reconstruction. Results: Quantitative histomorphometric data were assessed 10 weeks after injury. On post hoc analysis, the IL-4 bridge group demonstrated superior regeneration compared to bridge alone on fiber density (mean = 2,380 AE 297 vs. 1,680 AE 441 fibers/mm 2 , P = .05) and latency time (mean = 2.9 ms AE 0.6 ms vs. 3.6 ms AE 0.3 ms, P < .001). There was significantly greater regeneration in the IL-4 bridge group versus unreconstructed defect for total fiber and density measurements (P ≤ .05). Comparison of facial motor-evoked distal latencies between the IL-4 bridge group versus bridge alone revealed significant electrophysiological improvement at week 8 (P = .02). Conclusions: Inflammation has been implicated in a variety of otolaryngologic disorders. This study demonstrates that placement of a multichannel bridge with lentivirus encoding IL-4 improves regenerative outcomes following facial nerve gap injury in rodents. This effect is likely mediated by promotion of an anti-inflammatory environment, and these findings may inform future therapeutic approaches to facial nerve injury.

The Role of the IL-4 Signaling Pathway in Traumatic Nerve Injuries

“…Nerve conduit repair models showed greater axon regeneration and axon density across a nerve gap when using IL-4-filled conduits compared to no drug within a conduit. 62,63 Additionally, IL-4 treatment increased SC migration into the conduit and was associated with increased numbers of macrophages in the nerve. Upon further analysis, this greater macrophage population was composed primarily of M2 macrophages and had a decreased M1 macrophage ratio compared to controls.…”