Estrogen Reduces Lung Inflammation and Protects Female Mice From Severe Influenza

NIAID Now | January 25, 2019

Estrogens are reproductive hormones that influence a range of processes in both females and males. Estriol (E3), one of three forms of estrogen that females produce, has wide-ranging activity in diverse tissue types. Because E3 has relatively weak effects on breast and uterine tissues, treating women with E3 is associated with a lower risk of breast and uterine cancer compared with other forms of estrogen. E3 also has anti-inflammatory effects and can reduce the severity of autoimmune diseases such as multiple sclerosis. Despite these properties, little is known about the role of E3 in infectious diseases.

Since influenza A virus (IAV) infection causes excessive inflammation in the lungs, NIAD-funded researchers investigated the effects of E3 treatment on influenza infection in mice. Treating female mice with E3 reduced total lung inflammation and improved disease outcome following infection with nonlethal doses of IAV. Further, E3 treatment reduced the activity of genes in the lungs that code for inflammatory molecules. These changes in gene expression resulted in reduced movement of immune cells into the lungs and other immune changes associated with reduced disease severity. Despite these alterations in immune responses, viral replication and clearance from the body did not change with E3 treatment, suggesting that E3-treated mice maintained enough antiviral immunity despite reduced overall inflammation.

Increasing evidence suggests that the activity of estrogens may contribute to some of the differences in disease severity observed between males and females. Although the mechanisms of estrogen-modulated impacts on the course of disease are complex and vary between tissues, overall evidence indicates that estrogen-dependent effects can impact immune responses. Specifically, results from this study suggest that treatment with E3 is protective during IAV infection, and that E3 may have broad potential as a therapy for both infectious and noninfectious inflammatory diseases.

Reference: Vermillion MS. et al. Estriol Reduces Pulmonary Immune Cell Recruitment and Inflammation to Protect Female Mice From Severe Influenza. Endocrinology. 2018 Sep 1;159(9):3306–3320.

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