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

PROBLEM: Influenza infection severity may be mediated by estradiol and/or progesterone. METHOD OF STUDY: An exploratory study was designed to evaluate 17-ß-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-ß-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-ß-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-ß-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-ß-estradiol. CONCLUSION: Estradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection.