Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females

Following are Excerpts from the Peer-Reviewed Research Article

SUMMARY

Worldwide, the use of hormonal contraceptives is on the rise as a primary intervention for improving women’s health outcomes through reduced maternal mortality and increased childhood survival. There are many hormone contraceptive formulations, all of which contain some form of progesterone.

Although the effects of hormone contraceptives and progesterone, specifically, have been evaluated in the context of infections of the reproductive tract, the effects of progesterone at other mucosal sites, including the respiratory tract have not been systematically evaluated.

We have made the novel observation that administration of progesterone to female mice depleted of progesterone confers protection against both lethal and sublethal influenza A virus infection. In particular, progesterone reduces pulmonary inflammation, improves lung function, repairs the damaged lung epithelium, and promotes faster recovery following influenza A virus infection.

Progesterone causes protection against severe outcome from influenza by inducing production of the epidermal growth factor, amphiregulin, by respiratory epithelial cells.

This study provides insight into a novel mechanistic role of progesterone in the lungs and illustrates that sex hormone exposure, including through the use of hormonal contraceptives, has significant health effects beyond the reproductive tract.

Progesterone's Activity on Immune Cells & Non-Immune Cells

Natural Progesterone (P4) produced by the ovaries during reproductive cycles, or synthetic Progesterone analogues found in contraceptives (progestins), signal primarily through progesterone receptors present on many cells in the body, including immune cells (e.g., NK cells, macrophages, dendritic cells (DCs), and T cells) as well as non-immune cells, such as epithelial cells, endothelial cells, and neuronal cells.

Studies show that Progesterone can alter the immune environment and promote homeostasis by decreasing inflammation and inducing anti-inflammatory responses.

For example, in the presence of Progesterone, macrophages and dendritic cells have a lower state of activation, produce higher levels of anti-inflammatory cytokines, such as IL-10, and produce lower amounts of pro-inflammatory cytokines, such as IL-1β and TNF-α…

HIGHLIGHTS

*Progesterone limits lung pathology and protects female mice against lethal Influenza A Virus infection

*Progesterone promotes a repair environment in the lungs during lethal Influenza A Virus infection

*Progesterone accelerates long-term pulmonary recovery during sub-lethal Influenza A Virus infection

*Progesterone accelerates wound healing and increases production of AREG by respiratory epithelial cells

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