N‐Acetyl‐cysteine inhibition of encephalomyelitis Theiler’s virus‐induced nitric oxide and tumour necrosis factor‐\alpha production by murine astrocyte cultures
Affiliations: Neural Plasticity Unit, Instituto Cajal, CSIC, Madrid, Spain | Servicio de Bioquímica, Hospital de la Paz, Madrid, Spain | Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad Complutense Madrid, Spain
Note: [] Address correspondence to: Carmen Guaza, Neural Plasticity Unit, Instituto Cajal, CSIC, Avda Dr. Arce 37, 28002 Madrid, Spain. Fax: +34 1 585 4754; E‐mail: CGJB cajal.csic.es.
Abstract: The pathological mechanisms that cause central nervous system (CNS) dysfunction in most neurological diseases are not well established. Theiler’s murine encephalomyelitis virus (TMEV) is known to interact with cells of the CNS and its intracerebral inoculation to susceptible mice strains causes neurological disorders resembling multiple sclerosis (MS). In this study, we reported that primary astrocyte cultures from SJL/J susceptible mice when infected with TMEV released important amounts of nitrites (NO_{2}^{-}) to the culture medium, as measured in the supernatants 24 hours after infection. In addition, we observed an increment in the production of tumour necrosis factor alpha (TNF‐\alpha) by susceptible SJL/J strain derived astrocytes infected with TMEV. The treatment with the thiolic antioxidant N‐acetyl‐cysteine partially suppressed the virus‐stimulated production of nitric oxide and TNF‐\alpha, in a dose response fashion. These results indicate that during viral infection astrocytes are an important cellular source of nitric oxide and TNF‐\alpha, substances which play important roles during CNS inflammatory events. The effects of the antioxidant N‐acetyl‐cysteine, modulating the production of the above compounds by TMEV‐infected astrocytes may be a significant factor in preventing CNS demyelination.
