Uncoupling of interleukin-6 from its signalling pathway by dietary n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice.
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.
Mingam
Rozenn
R
Psychoneuroimmunologie, Nutrition et Genetique, PsyNuGen, INRA 1286, CNRS 5226, Université Bordeaux 2, Bordeaux, France.
Moranis
Aurélie
A
Bluthé
Rose-Marie
RM
De Smedt-Peyrusse
Véronique
V
Kelley
Keith W
KW
Guesnet
Philippe
P
Lavialle
Monique
M
Dantzer
Robert
R
Layé
Sophie
S
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001933:Brain Stem / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004042:Dietary Fats, Unsaturated / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D055809:Illness Behavior / Q000502:physiology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012919:Social Behavior
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse