title: Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome.
abstract: BACKGROUND
  Chronic Fatigue Syndrome (CFS) is a neuroimmunoendocrine disease affecting about 1% of the US population, mostly women. It is characterized by debilitating fatigue for six or more months in the absence of cancer or other systemic diseases. Many CFS patients also have fibromyalgia and skin hypersensitivity that worsen with stress. Corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted under stress, activate mast cells (MC) necessary for allergic reactions to release inflammatory mediators that could contribute to CFS symptoms.
  
  
  OBJECTIVE
  To investigate the effect of isoflavones on the action of polyinosinic:polycytidylic acid (poly(I:C)), with or without swim stress, on mouse locomotor activity and inflammatory mediator expression, as well as on human MC activation.
  
  
  METHODS
  Female C57BL/6 mice were randomly divided into four groups: (a) control/no-swim, (b) control/swim, (c) polyinosinic:polycytidylic acid (poly(I:C))/no swim, and (d) polyinosinic:polycytidylic acid (poly(I:C))/swim. Mice were provided with chow low or high in isoflavones for 2 weeks prior to ip injection with 20 mg/kg poly(I:C) followed or not by swim stress for 15 minutes. Locomotor activity was monitored overnight and animals were sacrificed the following day. Brain and skin gene expression, as well as serum levels, of inflammatory mediators were measured. Data were analyzed using the non-parametric Mann-Whitney U-test.
  
  
  RESULTS
  Poly(I:C)-treated mice had decreased locomotor activity over 24 hours, and increased serum levels of TNF-α, IL-6, KC (IL-8/CXCL8 murine homolog), CCL2,3,4,5, CXCL10, as well as brain and skin gene expression of TNF, IL-6, KC (Cxcl1, IL8 murine homolog), CCL2, CCL4, CCL5 and CXCL10. Histidine decarboxylase (HDC) and NT expression were also increased, but only in the skin, over the same period. High isoflavone diet reversed these effects.
  
  
  CONCLUSIONS
  Poly(I:C) treatment decreased mouse locomotor activity and increased serum levels and brain and skin gene expression of inflammatory mediators. These effects were inhibited by isoflavones that may prove useful in CFS.
authors.affiliation: Department of Integrative Physiology and Pathobiology, Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA. mvasiadi@gmail.com.|Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA. mvasiadi@gmail.com.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Vasiadi
authors.affiliation: Department of Neuroscience, Tufts University, School of Medicine, Boston, MA, USA. jennifer.newman@tufts.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Newman
authors.affiliation: Department of Integrative Physiology and Pathobiology, Molecular Immunopharmacology and Drug Discovery Laboratory, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA. theoharis.theoharides@tufts.edu.|Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA. theoharis.theoharides@tufts.edu.|Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA. theoharis.theoharides@tufts.edu.
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015673:Fatigue Syndrome, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011070:Poly I-C / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013550:Swimming / Q000502:physiology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D007529:Isoflavones; D011070:Poly I-C