Estradiol and progesterone influence on influenza infection and immune response in a mouse model

Abstract

Problem Influenza infection severity may be mediated by estradiol and/or progesterone. Method of Study An exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection, and examine immune mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Treatment groups included 17-β-estradiol, progesterone, ovariectomy, and pregnancy. Mice were assessed for morbidity and mortality. Toll-like receptor gene studies and airspace cell differentials were performed. Results Onset of morbidity was earlier, and morbidity duration greater for progesterone. Absence of morbidity/mortality and overall survival was greater for 17-β-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-β-estradiol. Pregnant mouse data demonstrate significant mortality during the period of increased progesterone. Select immune cell markers demonstrate patterns of regulation that may promote proper immune response to influenza infection for 17-β-estradiol. Conclusions Estradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection.

Influenza Pathogenesis: The Effect of Host Factors on Severity of Disease

“…Like estrogen, the effects of progesterone on IAV disease outcome are also inconclusive. Progesterone treatment prior to infection reduced excessive pulmonary inflammation, improved lung function, and promoted lung epithelium repair and faster recovery in female mice following IAV infection (63), whereas in a second study, onset of and duration of morbidity was earlier and greater following progesterone treatment (64). Collectively, these data illustrate that sex hormones modulate the immune response and, therefore, the outcome after IAV infection.…”

Sex and sex steroids impact influenza pathogenesis across the life course

“…Synthetic analogs of P4, termed progestins, are used as hormonal contraceptives. In C57BL/6 mice infected with IAV, treatment with either P4 or LNG prevents severe outcome by decreasing pulmonary inflammation and promoting faster recovery during a primary infection (31,60); in contrast, studies utilizing outbred CD-1 mice report minimal effects of P4 morbidity, mortality, and pulmonary inflammation following IAV infection (61). P4based treatments also promote pulmonary repair following clearance of IAVs by elevating levels of TGF-β, IL-6, IL-22 and increasing numbers of regulatory CD39+ Th17 cells in the lungs.…”

The intersection of sex and gender in the treatment of influenza

“…In C57BL/6 mice infected with IAV, treatment with either progesterone (P4) or a synthetic progestin, leovonorgestrel (LNG), prevents severe outcome by decreasing pulmonary inflammation and promoting faster recovery during a primary infection [26,39]; in contrast, studies utilizing outbred CD-1 mice report minimal effects of P4 morbidity, mortality, and pulmonary inflammation following IAV infection [40]. P4-based treatments also promote pulmonary repair following clearance of IAVs by elevating levels of TGF-β, IL-6, IL-22 and increasing numbers of regulatory CD39+ Th17 cells in the lungs.…”