High‐dose IgG suppresses local inflammation and facilitates functional recovery after olfactory system injury

OBJECTIVE: Head trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti‐inflammatory treatment using steroids or anti‐cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high‐dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury. METHODS: Olfactory nerve transection (NTx) was performed in OMP‐tau‐lacZ mice to establish injury models. High‐dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X‐gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test. RESULTS: High‐dose IgG‐injected mice showed significantly smaller areas of injury‐associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG‐injected mice. INTERPRETATION: These findings suggest that high‐dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.