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

Shock. 2001 Nov;16(5):340-3. doi: 10.1097/00024382-200116050-00003.


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.

MeSH terms

  • Adult
  • Body Mass Index
  • Cytokines / blood*
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Estradiol / blood
  • Estradiol / pharmacology
  • Estradiol / physiology*
  • Female
  • Humans
  • Leukocyte Count
  • Lipopolysaccharides / pharmacology*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • Progesterone / blood
  • Sex Characteristics*
  • Testosterone / blood


  • Cytokines
  • Lipopolysaccharides
  • Testosterone
  • Progesterone
  • Estradiol