When it comes to immunity, men may not have been dealt an equal hand. The latest study by Dr. Maya Saleh, of the Research Institute of the McGill University Health Centre and McGill University, shows that women have a more powerful immune system than men. In fact, the production of estrogen by females could have a beneficial effect on the innate inflammatory response against bacterial pathogens. The results were published today in the Proceedings of the National Academy of Sciences.

More specifically, estrogen naturally produced in women seems to block the production of an enzyme called Caspase-12, which itself blocks the inflammatory process. The presence of estrogen would therefore have a beneficial effect on innate immunity, which represents the body's first line of defence against pathogenic organisms. "These results demonstrate that women have a more powerful inflammatory response than men," said Dr. Saleh. 

This study was conducted on mice that lack the Caspase-12 gene, meaning that the mice were extremely resistant to infection. The human Caspase-12 gene was implanted in a group of male and female mice, yet only the males became more prone to infection. "We were very surprised by these results, and we determined that the estrogen produced by the female mice blocked the expression of the human Caspase-12 gene," explained Dr. Saleh. "We were also able to locate where the estrogen receptor binds on the gene in order to block its expression, which indicates that the hormone exerts direct action in this case."

Since these experiments were conducted using a human gene, the researchers consider these results to be applicable to humans. This feature of the female innate immune system might have evolved to better protect women's reproductive role.

The positive effect of natural estrogen on our resistence to infection is also exhibited with synthetic hormones such as 17-beta-estradiol. This finding might therefore open the door to new therapeutic applications that reinforce the immune system, but a question remains: will men be amenable to the idea of being treated with an exclusively female hormone?

This study was supported by grants from the Canadian Institutes for Health research and the Canadian Foundation for Innovation.

Dr. Maya Saleh is a researcher with the Critical Care Division and the Centre for the Study of Host Resistance at the Research Institute of the McGill University Health Centre (MUHC) as well as an assistant professor with McGill University's Faculty of Medicine.

This project is a collaboration between the laboratory of Dr Maya Saleh at the Centre for the Study of Host Resistance at the Research Institute of the MUHC, Montreal, with Garabet Yeretssian, Karine Doiron and Wei Shao, the laboratories of Dr Blair R. Leavitt and Michael R. Hayden both at the Centre of Molecular Medicine and Therapeutics, Vancouver, and the laboratory of Dr Donald W. Nicholson at Merck Research Laboratories, USA.

The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec.