Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model.
Clinical studies demonstrate a better outcome of sepsis in females. Elevated estrogen levels and plasma cytokine imbalance occur in septic patients. We propose that gender-different cytokine secretion by the peripheral blood mononuclear cells (PBMCs) in sepsis determines the clinical outcome. A 2 x 10(6) PBMC sample from healthy volunteers (10 males and 10 females) was incubated with 1 ng/mL of lipopolysaccharide (LPS), estradiol (E2; 0, 0.03, 0.3, 3.0, 30 ng/mL), or 1 ng/mL of LPS + E2 (0, 0.03, 0.3, 3.0, 30 ng/ml), and supernatant cytokine levels were measured. Tumor necrosis factor alpha (TNF alpha) and interleukin (IL)-6 production by PBMCs from both sexes was time-dependently stimulated by LPS. At 6 h after LPS challenge, the TNF alpha level of male PBMCs was significantly higher but IL-6 secretion by female PBMCs was higher (two-way ANOVA: P < 0.05). E2 alone stimulated cytokine secretion by male PBMCs. Addition of the same E2 concentration as in sepsis patients' plasma modulated LPS-induced cytokine production. No significant sex differences in LPS-stimulated TNF alpha or IL-6 secretion by PBMCs were found, but IL-10 secretion by male PBMCs was significantly suppressed. This study demonstrated a gender difference in PBMCs responsiveness to LPS and E2 stimulation and E2-modulated cytokine secretion. In this PBMCs model of sepsis, only the supernatant IL-10 level was significantly lower in males. These ex vivo findings may partially explain the mechanism underlying the poorer outcome of male sepsis patients.
Asai
K
K
Department of Surgery, University of Tokyo, 3-28-6 Mejirodai Bunkyo-ku, Tokyo, Japan, 112-8688.
Hiki
N
N
Mimura
Y
Y
Ogawa
T
T
Unou
K
K
Kaminishi
M
M
D000328:Adult; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000097:blood; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood
D016207:Cytokines; D008070:Lipopolysaccharides; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol