title: Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6.
abstract: Autism spectrum disorders (ASDs) have been associated with brain inflammation as indicated by microglia activation, as well as brain expression and increased plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF). Here we report that serum levels of IL-6 and TNF were elevated (61.95 ± 94.76 pg ml(-1) and 313.8 ± 444.3 pg ml(-1), respectively) in the same cohort of patients with elevated serum levels of corticotropin-releasing hormone (CRH) and neurotensin (NT), while IL-9, IL-31 and IL-33 were not different from controls. The elevated CRH and NT levels did not change after treatment with a luteolin-containing dietary formulation. However, the mean serum IL-6 and TNF levels decreased significantly (P=0.036 and P=0.015, respectively) at the end of the treatment period (26 weeks) as compared with levels at the beginning; these decreases were strongly associated with children whose behavior improved the most after luteolin formulation treatment. Our results indicate that there are distinct subgroups of children within the ASDs that may be identifiable through serum levels of IL-6 and TNF and that these cytokines may constitute distinct prognostic markers for at least the beneficial effect of luteolin formulation.
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tsilioni
authors.affiliation: Department of Pediatrics, Athens University School of Medicine, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Taliou
authors.affiliation: Second Department of Psychiatry, Attikon General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Francis
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.|Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA.|Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA.|Department of Integrative Physiology and Pathobiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000067877:Autism Spectrum Disorder / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy / Q000523:psychology; D001526:Behavioral Symptoms / Q000175:diagnosis / Q000178:diet therapy; D002648:Child; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004035:Diet Therapy / Q000379:methods*; D005260:Female; D005526:Food, Formulated; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood*; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D009496:Neurotensin / Q000097:blood; D011379:Prognosis; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009496:Neurotensin; D003346:Corticotropin-Releasing Hormone; D047311:Luteolin