[Immunological determinants and the spread of viral infection in facial nerve paralysis induced by herpes simplex virus in mice].

Herpes simplex virus type 1 (HSV-1) infection of the facial nerve has been strongly suggested as a cause of Bell's palsy. The author's group have produced a transient and homolateral facial paralysis in Balb/c mice by inoculating HSV-1 onto the auricle, simulating the symptoms of Bell's palsy. To clarify whether and how age and specific immunity against HSV-1 are involved in the pathogenesis of facial nerve paralysis, age dependent susceptibility to the virus and passive immunization with anti-HSV-1 antibody or immunized splenic T cells were investigated in a mouse model system. Following inoculation of HSV-1 into 3-week-old mice, 80% of the animals died whereas only 13% of 4-to 5-week-old mice died, and 50% developed facial nerve paralysis 1 week after the inoculation. No 6-week-old mice died and 6% developed facial nerve paralysis. Although all mice showed seroconversion of neutralizing antibody regardless of the presence of facial nerve paralysis, six-week-old mice and 4-week-old mice without facial nerve paralysis produce higher titers of anti-HSV-1 antibody than 4-week-old-mice with facial nerve paralysis. These results suggested that the age and the immunological potential of mice are closely related to the pathogenesis of facial nerve paralysis. Passive transfer of either anti-HSV-1 antibody or HSV-1 immunized splenic T cells into 4-week-old mice prevented development of facial nerve paralysis and death if they were transferred within 3 hours postinoculation. However, a similar transfer 48 or 96 hours after HSV-1 inoculation did not produce such protection. HSV-1 DNAs were detected in the facial nerve as early as 48 hours postinoculation by polymerase chain reaction (PCR). These results indicate that the passive immunization, providing both cellular and humoral immunity, is effective for preventing facial nerve paralysis if performed before virus infects the facial nerve. The nervous system has a blood-nerve barrier (BNB) which privileges it from the peripheral immune system. Therefore, once the virus infects the facial nerve, passive immunity transferred from peripheral vessel might be excluded from the virus or virus-infected cells unless the BNB is broken down. Bell's palsy is thought to occur during the course of HSV-1 latency in the geniculate ganglion. If we could reactivate latently infected virus and produce facial nerve paralysis again in the animal model, this might provide clues to clarify not only the pathological mechanism of Bell's palsy but also the interaction between immune system and virus reactivation.