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

• DOI: 10.1371/journal.ppat.1005840
• Publication Date: 2016-09-15T17:39:42Z
• Authors: Olivia J. Hall; Nathachit Limjuny...; Meghan S. Vermillion; Dionne P. Robinson; Nicholas Wohlgemuth; Andrew Pekosz; Wayne Mitzner; Sabra L. Klein
• Keywords: Mice, Knockout; 0301 basic medicine; QH301-705.5; Apyrase; RC581-607; Amphiregulin; 3. Good health; Mice; 03 medical and health sciences; Orthomyxoviridae Infections; Antigens, CD; Influenza A virus; Animals; Cytokines; Th17 Cells; Female; Immunologic diseases. Allergy; Biology (General); Lung; Research Article

Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside reproductive tract have not been evaluated. Administration exogenous (at concentrations that mimic luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal sublethal influenza A virus (IAV) infection. Progesterone treatment altered inflammatory environment lungs, but had no load. promoted faster recovery by increasing TGF-β, IL-6, IL-22, numbers regulatory Th17 cells expressing CD39, cellular proliferation, reducing protein leakage into airway, improving pulmonary function, upregulating epidermal growth factor amphiregulin (AREG) in lungs. rAREG females improved IAV Progesterone-treatment AREG-deficient could restore protection, indicating progesterone-mediated induction AREG caused lungs accelerated Repair production damaged respiratory epithelial cell cultures vitro was increased progesterone. Our results illustrate is a critical host mediating tissue following infection, which has important implications for women's health.