Aicardi-Goutières syndrome (AGS) presents as a severe autosomal recessively inherited neurological
brain disease. Clinical and
neurological manifestations closely resemble those of congenital
viral infection and are generally attributed to a perturbation of innate immunity including a long lasting
lymphocytosis and production of
interferon-alpha (IFNalpha) in the central nervous system. To clarify the innate immune response evoked in these diseases, we used a 30-mer multiplexed luminex system to measure multiple
cytokines and
growth factors in the cerebrospinal fluid and serum of patients with AGS and
viral meningitis or
encephalitis, and febrile controls in whom
infection could not be substantiated. In addition to the previously described IFNalpha, both AGS and
viral diseases were characterized by expression of CXCL10 and CCL2. In contrast to AGS,
viral infection resulted in high levels of
IL-6 and CXCL8 in the CNS. Postmortem immunohistochemical staining of brain sections showed that in both AGS and
viral CNS infection, astrocytes were responsible for the production of
cytokines and not the infiltrating leukocytes. In summary, our data indicate that astrocytes are the predominant cell type responsible for the production of IFNalpha and CXCL10 in AGS. Whereas IFNalpha is assumed to be involved in the neurodegeneration, calcifications and
seizures in AGS, CXCL10 may act as the
chemoattractant responsible for the influx of activated lymphocytes into the brain. The lack of the inflammatory
cytokines IL-6 and CXCL8 in AGS suggest that the neuroinflammatory reaction in this disease is distinct from
viral disease.