Age and testosterone mediate influenza pathogenesis in male mice

Landon G. Vom Steeg, Meghan S. Vermillion, Olivia J. Hall, Ornob Alam, Ross McFarland, Haolin Chen, Barry Zirkin, Sabra L. Klein

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza severity increases with age, with hospitalization and mortality rates during seasonal influenza epidemics being higher in older men than agematched women. As it is known that with age, circulating testosterone levels decline in males, we hypothesized that reduced testosterone contributes to age-associated increases in influenza severity. A murine model was used to test this hypothesis. As in men, testosterone concentrations were lower in aged (18 mo) than young (2 mo) male C57BL/6 mice. Following inoculation with influenza A virus (IAV), aged males experienced greater morbidity, clinical disease, and pulmonary inflammation than young males, and had lower neutralizing and total anti-influenza IgG antibody responses. Peak titers of virus in the lungs did not differ between aged and young males, but virus clearance was delayed in aged males. In young males, removal of the gonads increased—whereas treatment of gonadectomized males with testosterone reduced—morbidity, clinical illness, and pulmonary pathology, but viral replication was not altered by hormone manipulation in young males. Treatment of aged males with testosterone improved survival following infection but did not alter either virus replication or pulmonary pathology. These results indicate that low concentrations of testosterone, whether induced surgically in young males or naturally occurring in aged males, negatively impact the outcome of influenza.

Original languageEnglish (US)
Pages (from-to)L1234-L1244
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number6
DOIs
StatePublished - 2016

Keywords

  • 2009 H1N1
  • Androgen
  • Elderly
  • Pulmonary inflammation
  • Sex steroids

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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