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Sexual differences in the inflammatory response
Submit responseIn a recent issue, Blood published a paper 1 considering sexual differences in the inflammatory response, showing more efficient acute inflammatory responses in female mice. For many years, many papers have proposed to their readers gender differences in the responses to acute or chronic infectious diseases 2-4. Until now, this dimorphism was not clearly explained by hormonal, nor disease-related factors. We recently published three papers 5-7 regarding the sexual differences in inflammation, showing that boys have a worse prognosis in acute inflammatory diseases whereas girls have more serious clinical complications in chronic inflammatory diseases. Inflammation seems to be the crucial factor in the different outcomes, and the hormonal climate doesn't completely explain it since the phenomenon spans all ages, from premature infants to old age. Even prepubescent girls and boys with low levels of steroid hormones show this pattern of dimorphic responses in acute pneumonia or in chronic diseases such as cystic fibrosis. Several genes located on X chromosome code for molecule involved in inflammation. Moreover, if allelic exclusion of one X chromosome occurs, 10-15 % of genes from the silenced X chromosome escape this inhibition. The similarities observed between males and Turner syndrome females (XO) after exposure to endotoxin suggest there are differences in gene expression between monosomy and disomy with an inactivated X chromosome that contribute to the dimorphism. Considering enhanced inflammation in females, it could be postulated that cytokine production would be higher in females. However, many studies have reported production of higher levels by male immune cells studied ex vivo. High levels of IL-6 observed in males appear to correlate with shorter lifespan. IL-6, TNF and IL-1 are inter-dependent and males have a significantly lower coefficient of variation (slope) than females for this relationship.
References
1. Ramona S. Scotland, Melanie J. Stables et al. Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice. Blood.2011 ; 118: 5918-5927
2. Kaplan V, Angus DC, Griffin MF et al. Hospitalized community-acquired pneumonia in the elderly. Am J Resp Crit Care Med 2002; 165: 766-72.
3. Watson RS, Carcillo JA, Linde-Zwirbel WT et al. The epidemiology of severe sepsis in children in the United States. Am J Resp Crit Care Med 2002; 167: 695-701.
4. Han MK, Postma D, Mannino DM et al. Gender and chronic obstructive pulmonary disease: why it matters. Am J Respiratory Crit Care Med 2007; 176: 1179-84.
5. Casimir GJ, Mulier S, Hanssens L et al. Gender differences in inflammatory markers in children. Shock 2010; 33 :258-62.
6. Casimir GJ, Mulier S, Hanssens L et al. Chronic inflammatory diseases in children are more severe in girls. Shock 2010; 34: 23-26.
7. Casimir GJ, Heldenbergh F, Hanssens L et al. Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children. J Inflamm (London) 2010; 7: 28.
Conflict of Interest:
None declared
