Sexual dimorphism in experimental endotoxaemia
Ellen L Hughes, Julia C Buckingham & Felicity N E Gavins
Sexual dimorphisms have been observed in numerous diseases, particularly those associated with inflammation. Generally, males are more at risk of developing infection and subsequent mortality1, whilst women are more prone to develop autoimmune disorders2. Hormones, particularly oestrogens, are thought to play a significant role effecting these dimorphisms, and oestrogens have been shown to reduce the severity of sepsis3.
In order to investigate the protective effect of oestrogens in sepsis, a murine model of experimental endotoxaemia was used. Intact male C57BL/6 mice or ovariectomised female C57BL/6 mice treated for 8 days 17β-oestradiol (40 ng/mouse, s.c.) or a corresponding volume of the vehicle were used. Mice were treated with LPS (10 μg/mouse) or saline vehicle. After 2 h, they were anaesthetised, the mesentery was exteriorised and leukocyteendothelium interactions in post-capillary venules were quantified by intravital microscopy.
LPS caused an inflammatory response in male animals characterised by increased cell flux and adherent and emigrated leukocytes, and reduced leukocyte rolling velocity. In females, LPS caused no change in cell flux, rolling or emigration. Ovariectomy caused an increase in adherent cells, with both control and LPS-treated groups showing significantly more adherent cells than male counterparts. In addition, baseline levels of emigrated cells in oestrogen-deficient females were increased above males. Females given oestrogen replacement showed no alterations in baseline compared to males, and additionally had no significant increase in adherent cells following LPS.
These novel data demonstrate a protective effect of oestrogen in murine experimental endotoxaemia may further help explain why the incidence of sexual dimorphism in inflammatory disease reduced after the age of the menopause.
1. Klein S. Neurosci Biobehav Rev 2000 24 627.
2. Beeson P. Am J Med 1994 96 457.
3. Erikoğlu M. et al. Surg Today 2005 35 467.