In the recent 2009 H1N1 pandemic young adult women experienced greater mortality than age-matched men. Murine models show worse outcomes in adult females compared to males. So estrogen is bad for influenza, right? Not so fast! In a recent AJP Lung paper that has garnered media attention (http://www.sciencedaily.com/releases/2016/01/160112093424.htm), Dr. Sabra Klein and colleagues report that estrogen or compounds with estrogen-like activity actually reduce influenza virus replication in primary human nasal epithelial cells—but only in those from female, not male, donors. The effect is mediated through the 2nd genomic estrogen receptor, ER-beta, since neither of the other two ER receptors (ER-alpha or GPR30) were expressed in the nasal epithelial cells, and an ER antagonist could block estrogen’s effects. Transcriptome profiling showed marked down-regulation of zinc-finger proteins, an intriguing clue to possible molecular mechanisms for both the anti-proliferative effect and the sex selectivity . This work expands on past studies from the Klein lab showing that pharmacologic or high levels of estrogen can have beneficial effects on influenza outcome in mouse models, while recognizing that normal low levels may have paradoxical pro-inflammatory or harmful effects. The biphasic nature of hormone effects is well known, and these data are a fascinating addition to the important role of sex hormones in modulating outcomes in infectious disease.
To find out more about this interesting study, please check out the full text of this article. It is available for free on the AJP-Lung website, even for those with no subscription to APS journals:
Dr. Lester Kobzik