Blockade of interleukin-6 receptor suppresses inflammatory reaction and facilitates functional recovery following olfactory system injury.

We previously reported that anti-inflammatory treatment with steroids improves recovery outcome in an olfactory nerve injury model. Clinically, however, steroid administration is not recommended in the acute phase of head injury because of concerns regarding side effects and no evidence of its efficacy. Recently, it has been reported that interleukin-6 (IL-6) plays an important role in the inflammatory reaction. The present study investigates if anti-IL-6 receptor (IL-6R) antibody can facilitate functional recovery in the olfactory system following injury. Rat anti-mouse IL-6R antibody (MR16-1) was intraperitoneally injected to severe olfactory nerve injury model mice immediately after the nerve transection (NTx). Histological assessment of recovery within the olfactory bulb was made at 5-70 days. X-gal staining labeled the degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. MR16-1-injected animals showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential testing showed improved functional recovery in MR16-1-injected mice. These findings suggest that blockade of IL-6R could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

[Clinical diagnosis of the olfactory nerve transport function].

Nasal administration of macromolecular drugs (peptides, nanoparticles) has a possibility to enable a drug delivery system beyond the blood brain barrier via olfactory nerve transport. Basic research on nasal drug delivery to the brain has been well studied. However, evaluation of the olfactory nerve transport function in patients with olfactory disorders has yet to be done, although such an evaluation is important in selecting candidates for clinical trials. Current olfactory function tests are useful for the analysis of olfactory thresholds in olfaction-impaired patients. However, the usefulness of using the increase in olfactory thresholds in patients as an index for evaluating olfactory nerve damage has not been confirmed because of the difficulty in directly evaluating the viability of the peripheral olfactory nerves. Nasally administered thallium-201 migrates to the olfactory bulb, as has been shown in healthy volunteers. Furthermore, transection of olfactory nerve fibers in mice significantly decreases migration of nasally administered thallium-201 to the olfactory bulb. The migration of thallium-201 to the olfactory bulb is reduced in patients with impaired olfaction due to head trauma, upper respiratory tract infections, and chronic rhinosinusitis, relative to the values in healthy volunteers. Nasally administrating thallium-201 followed by single photon emission computed tomography, X-ray computed tomography and magnetic resonance imaging might be useful in choosing candidates for clinical trials of nasal drug delivery methods to the brain.