title: Sex differences in monocyte activation in systemic lupus erythematosus (SLE).
abstract: BACKGROUND
  TLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis.
  
  
  METHODS
  Human blood samples from 27 healthy male controls, 32 healthy female controls, and 25 female patients with SLE matched for age and race were studied. Monocyte activation was tested by flow cytometry and ELISA, including subset proportions, CD14, CD80 and CD86 expression, the percentage of IL-6-producing monocytes, plasma levels of sCD14 and IL-6, and urine levels of creatinine.
  
  
  RESULTS
  Monocytes were significantly more activated in women compared to men and in patients with SLE compared to controls in vivo. We observed increased proportions of non-classic monocytes, decreased proportions of classic monocytes, elevated levels of plasma sCD14 as well as reduced surface expression of CD14 on monocytes comparing women to men and lupus patients to controls. Plasma levels of IL-6 were positively related to sCD14 and serum creatinine.
  
  
  CONCLUSIONS
  Monocyte activation and TLR4 responsiveness are altered in women compared to men and in patients with SLE compared to controls. These sex differences may allow persistent systemic inflammation and resultant enhanced SLE susceptibility.
authors.affiliation: Department of Microbiology and Immunology, Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Microbiology and Immunology, Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Lumin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Lang
authors.affiliation: Department of Microbiology and Immunology, Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Gilkeson
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors