Objective. Since the level of interferon‐α (IFNα) is increased in the sera of patients with active systemic lupus erythematosus (SLE) and is detectable in the cerebrospinal fluid (CSF) of some SLE patients with neuropsychiatric manifestations, we investigated the contribution of IFNα to the pathogenesis of the neuropsychiatric manifestations of SLE.

Methods. IFNα levels were quantitated by radioimmunoassay in CSF and serum samples from 17 SLE patients with neuropsychiatric manifestations and 28 patients with SLE alone or SLE and other neurologic disorders.

Results. Levels of IFNα were increased in the CSF of 5 of 6 patients with lupus psychosis, and in 4 of these 5 patients, the levels in CSF were higher than those in serum. IFNα levels decreased when the manifestation of lupus psychosis subsided. In contrast, IFNα levels in CSF samples from patients with seizures alone were not increased. One patient with lupus psychosis died of complications of generalized seizures resulting from the SLE. At autopsy, we investigated whether IFNα protein or messenger RNA was detectable in the subject's brain. IFNα protein was immunohistochemically demonstrated in the neurons and in the microglia (focal accumulation), features not present in the brain tissues of subjects who died of other diseases.

Conclusion. These findings support the hypothesis that IFNα, possibly synthesized in the brain, is the cause of the manifestation of psychosis in patients with SLE.