title: Uncoupling of interleukin-6 from its signalling pathway by dietary n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice.
abstract: 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.
authors.affiliation: Psychoneuroimmunologie, Nutrition et Genetique, PsyNuGen, INRA 1286, CNRS 5226, Université Bordeaux 2, Bordeaux, France.
authors.forename: Rozenn
authors.initials: R
authors.lastname: Mingam
authors.forename: Aurélie
authors.initials: A
authors.lastname: Moranis
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Bluthé
authors.forename: Véronique
authors.initials: V
authors.lastname: De Smedt-Peyrusse
authors.forename: Keith W
authors.initials: KW
authors.lastname: Kelley
authors.forename: Philippe
authors.initials: P
authors.lastname: Guesnet
authors.forename: Monique
authors.initials: M
authors.lastname: Lavialle
authors.forename: Robert
authors.initials: R
authors.lastname: Dantzer
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
mesh_terms: 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
chemical_list: 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