Interdependent and independent roles of type I interferons and IL-6 in innate immune, neuroinflammatory and sickness behaviour responses to systemic poly I:C.
Brain Behav Immun
; 48: 274-86, 2015 Aug.
Article
en En
| MEDLINE
| ID: mdl-25900439
ABSTRACT
Type I interferons (IFN-I) are expressed in the brain during many inflammatory and neurodegenerative conditions and have multiple effects on CNS function. IFN-I is readily induced in the brain by systemic administration of the viral mimetic, poly IC (synthetic double-stranded RNA). We hypothesised that IFN-I contributes to systemically administered poly IC-induced sickness behaviour, metabolic and neuroinflammatory changes. IFN-I receptor 1 deficient mice (IFNAR1(-/-)) displayed significantly attenuated poly IC-induced hypothermia, hypoactivity and weight loss compared to WT C57BL/6 mice. This amelioration of sickness was associated with equivalent IL-1ß and TNF-α responses but much reduced IL-6 responses in plasma, hypothalamus and hippocampus of IFNAR1(-/-) mice. IFN-ß injection induced trivial IL-6 production and limited behavioural change and the poly IC-induced IFN-ß response did not preceed, and would not appear to mediate, IL-6 induction. Rather, IFNAR1(-/-) mice lack basal IFN-I activity, have lower STAT1 levels and show significantly lower levels of several inflammatory transcripts, including stat1. Basal IFN-I activity appears to play a facilitatory role in the full expression of the IL-6 response and activation of the tryptophan-kynurenine metabolism pathway. The deficient IL-6 response in IFNAR1(-/-) mice partially explains the observed incomplete sickness behaviour response. Reconstitution of circulating IL-6 revealed that the role of IFNAR in burrowing activity is mediated via IL-6, while IFN-I and IL-6 have additive effects on hypoactivity, but the role of IFN-I in anorexia is independent of IL-6. Hence, we have demonstrated both interdependent and independent roles for IFN-I and IL-6 in systemic inflammation-induced changes in brain function.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Interferón Tipo I
/
Interleucina-6
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Poli I-C
/
Conducta de Enfermedad
/
Inmunidad Innata
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Brain Behav Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
CEREBRO
/
PSICOFISIOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Irlanda