title: Gender differences in the inflammatory cytokine and chemokine profiles induced by binge ethanol drinking in adolescence.
abstract: Heavy binge drinking in adolescence can cause long-term cognitive and behavioral dysfunctions. Recent experimental evidence indicates the participation of immune system activation in the effects of ethanol in the adolescent brain and suggests gender differences. The present study aims to assess plasma cytokine and chemokine levels in male and female adolescents and young adults during acute alcohol intoxication and to correlate these results with the toll-like receptor 4 (TLR4) response. The potential role of the TLR4 signaling response was also assessed in plasma and prefrontal cortex (PFC) of adolescent wild-type and TLR4-knockout male and female mice with binge ethanol treatment. The results showed that alcohol intoxication increased the plasma levels of several cytokine and chemokine [interferon-γ, interleukin (IL)-10, IL-17A, IL-1β, IL-2, IL-4, IL-6, IL-8, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1α (MIP-1α)] and the upregulation of TLR4 mRNA levels occurred in intoxicated females, while elevation of colony-stimulating factor was only observed in the plasma of males. In wild-type female adolescent mice, intermittent ethanol treatment increased the levels of several cytokines (IL-17A and IL-1β) and chemokines (MCP-1, MIP-1α and fractalkine) in PFC and in serum (IL-17A, MCP-1 and MIP-1α), but significant differences in the fractalkine levels in PFC were observed only in male mice. No changes in serum or prefrontal cortex cytokine and chemokine levels were noted in ethanol-treated male or female TLR4-knockout mice. Our findings revealed that females are more vulnerable than males to inflammatory effects of binge ethanol drinking and suggested that TLR4 is an important target of ethanol-induced inflammation and neuroinflammation in adolescence.
authors.affiliation: Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe Research Center, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pascual
authors.affiliation: Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe Research Center, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Montesinos
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcos
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Spain.
authors.forename: Jorge-Luis
authors.initials: JL
authors.lastname: Torres
authors.affiliation: Emergency Department, University Hospital of Salamanca-IBSAL, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Costa-Alba
authors.affiliation: Computational Genomics Department, Príncipe Felipe Research Center, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Spain.
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Laso
authors.affiliation: Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe Research Center, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Guerri
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D063425:Binge Drinking / Q000097:blood* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012737:Sex Factors; D013030:Spain; D000066608:Underage Drinking; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; D018925:Chemokines; D016207:Cytokines; D000431:Ethanol
keywords: Adolescent humans; TLR4; adolescent mice; gender difference; inflammation