Uncoupling of interleukin-6 from its signalling pathway by dietary n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice
European Journal of Neuroscience. 2008-11-01; 28(9): 1877-1886
DOI: 10.1111/j.1460-9568.2008.06470.x
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1. Eur J Neurosci. 2008 Nov;28(9):1877-86. doi: 10.1111/j.1460-9568.2008.06470.x.
Uncoupling of interleukin-6 from its signalling pathway by dietary
n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice.
Mingam R(1), Moranis A, Bluthé RM, De Smedt-Peyrusse V, Kelley KW, Guesnet P,
Lavialle M, Dantzer R, Layé S.
Author information:
(1)Psychoneuroimmunologie, Nutrition et Genetique, PsyNuGen, INRA 1286, CNRS
5226, Université Bordeaux 2, Bordeaux, France.
Sickness behaviour is an adaptive behavioural response to the activation of the
innate immune system. It is mediated by brain cytokine production and action,
especially interleukin-6 (IL-6). Polyunsaturated fatty acids (PUFA) are essential
fatty acids that are highly incorporated in brain cell membranes and display
immunomodulating properties. We hypothesized that a decrease in n-3 (also known
as omega3) PUFA brain level by dietary means impacts on lipopolysaccharide
(LPS)-induced IL-6 production and sickness behaviour. Our results show that mice
exposed throughout life to a diet containing n-3 PUFA (n-3/n-6 diet) display a
decrease in social interaction that does not occur in mice submitted to a diet
devoid of n-3 PUFA (n-6 diet). LPS induced high IL-6 plasma levels as well as
expression of IL-6 mRNA in the hippocampus and cFos mRNA in the brainstem of mice
fed either diet, indicating intact immune-to-brain communication. However, STAT3
and STAT1 activation, a hallmark of the IL-6 signalling pathway, was lower in the
hippocampus of LPS-treated n-6 mice than n-3/n-6 mice. In addition, LPS did not
reduce social interaction in IL-6-knockout (IL-6-KO) mice and failed to induce
STAT3 activation in the brain of IL-6-KO mice. Altogether, these findings point
to alteration in brain STAT3 as a key mechanism for the lack of effect of LPS on
social interaction in mice fed with the n-6 PUFA diet. The relative deficiency of
Western diets in n-3 PUFA could impact on behavioural aspects of the host
response to infection.
DOI: 10.1111/j.1460-9568.2008.06470.x
PMCID: PMC2769572
PMID: 18973601 [Indexed for MEDLINE]