TY - JOUR
T1 - Age and testosterone mediate influenza pathogenesis in male mice
AU - Vom Steeg, Landon G.
AU - Vermillion, Meghan S.
AU - Hall, Olivia J.
AU - Alam, Ornob
AU - McFarland, Ross
AU - Chen, Haolin
AU - Zirkin, Barry
AU - Klein, Sabra L.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants AI112838 (to S. L. Klein) and NIH/NIAID training grant fellowship AI007417 to L. G. vom Steeg.
Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - 2009 H1N1
KW - Androgen
KW - Elderly
KW - Pulmonary inflammation
KW - Sex steroids
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U2 - 10.1152/ajplung.00352.2016
DO - 10.1152/ajplung.00352.2016
M3 - Article
C2 - 27815260
AN - SCOPUS:85006320114
SN - 1040-0605
VL - 311
SP - L1234-L1244
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 6
ER -