title: Sex differences in inflammatory cytokines and CD99 expression following in vitro lipopolysaccharide stimulation.
abstract: Sex influences the severity and evolution of various inflammatory conditions. Although many studies have demonstrated the role of sex hormones in immune response modulation, recent clinical data revealed significant sex differences in inflammatory markers in prepubertal children, suggesting a genetic contribution. We studied several immune functions depending on X-linked genes in healthy adults of both sexes: the respiratory burst of purified neutrophils, the CD99 and CD11b expression of stimulated leukocytes as markers of adhesion and diapedesis, and the production of inflammatory cytokines in whole blood after incubation with lipopolysaccharide for 24 h. The percentage of monocytes expressing CD99 was higher in men than in women, thus confirming the higher CD99 expression reported in males using reverse transcription-polymerase chain reaction. In addition, we observed a higher tumor necrosis factor α and tendency toward higher interleukin (IL) 6 production in men after lipopolysaccharide stimulation. These differences may contribute to the higher mortality reported in men with septic shock. Tumor necrosis factor α production significantly correlated with monocyte count, with men having a higher monocyte count than women. When cytokine levels were normalized to monocyte counts, a higher IL-8 production was found in women, which may explain the higher neutrophil count observed in girls with acute inflammatory diseases, because IL-8 is a major neutrophil chemoattractant. These sex differences regarding the activation of certain X-linked genes involved in innate immunity confirm our clinical observations, thus supporting the role of sex chromosomes in inflammatory response.
authors.affiliation: Department of Pulmonology, Allergology and Cystic Fibrosis, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium. nicolas.lefevre@huderf.be
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lefèvre
authors.forename: Francis
authors.initials: F
authors.lastname: Corazza
authors.forename: Jean
authors.initials: J
authors.lastname: Duchateau
authors.forename: Julie
authors.initials: J
authors.lastname: Desir
authors.forename: Georges
authors.initials: G
authors.lastname: Casimir
mesh_terms: D000071443:12E7 Antigen; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D039481:CD11b Antigen / Q000097:blood; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004906:Erythrocyte Count; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D016897:Respiratory Burst / Q000276:immunology / Q000502:physiology; D012727:Sex Characteristics; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood; D055815:Young Adult
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; D039481:CD11b Antigen; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; C509295:ITGAM protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha