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Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity.

ABSTRACT: The severity of influenza increases with age, with worse disease in aged males than females. Testosterone concentrations decline with age in males, which may impact influenza pathogenesis. Aged male mice were treated with testosterone or placebo and outcomes during influenza A virus (IAV) infection were compared with adult male mice. Aged males experienced greater morbidity and mortality than adult males, which was partially improved by testosterone treatment of aged males. Aged males cleared IAV from lungs slower than adult males, regardless of testosterone treatment. As compared with adult males, aged males experienced pulmonary, but not systemic, cytokine dysregulation, and delayed influx and contraction of IAV-specific CD8+ T cells in the lungs. Testosterone treatment in aged males partially restored pulmonary cytokine responses to levels consistent with adult males but did not alter the age-associated changes in IAV-specific CD8+ T cells. Testosterone only modestly improves outcomes of influenza in aged males.

SUBMITTER: Vom Steeg LG

PROVIDER: S-EPMC6876866 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity.

Vom Steeg Landon G LG Attreed Sarah E SE Zirkin Barry B Klein Sabra L SL

Cellular immunology 20190914

The severity of influenza increases with age, with worse disease in aged males than females. Testosterone concentrations decline with age in males, which may impact influenza pathogenesis. Aged male mice were treated with testosterone or placebo and outcomes during influenza A virus (IAV) infection were compared with adult male mice. Aged males experienced greater morbidity and mortality than adult males, which was partially improved by testosterone treatment of aged males. Aged males cleared IA ...[more]

PMID: 31540670

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Project description:BackgroundCardiovascular disease increases with age in both sexes. Treatment can require cardiac surgery, where the hearts are pre-treated with protective cardioplegic solution before ischemia and reperfusion (I/R). While endogenous estrogen is beneficial in I/R, whether testosterone is involved is uncertain and whether age modifies responses to I/R is unclear. We investigated sex- and age-specific differences in I/R injury in the hearts pre-treated with clinically relevant cardioplegic solution.MethodsThe hearts were isolated from young (6-9 months) and old (20-28 months) mice of both sexes and perfused (Langendorff) with Krebs-Henseleit buffer (15 min, 37 °C), followed by St. Thomas' two cardioplegia (6 min, 6-7 °C), global ischemia (90 min, 23-24 °C), and reperfusion (30 min, 37 °C). The hearts were perfused with triphenyltetrazolium chloride to quantify infarct area. Testosterone's role was investigated in gonadectomized (GDX, 6-9 months) male mice; serum testosterone and estradiol were measured with ELISA assays.ResultsLeft ventricular developed pressure (LVDP) recovered to 67.3 ± 7.4% in the old compared to 21.8 ± 9.2% in the young male hearts (p < 0.05). Similar results were seen for rates of pressure development (+dP/dt) and decay (-dP/dt). Infarct areas were smaller in the old male hearts (16.6 ± 1.6%) than in the younger hearts (55.8 ± 1.2%, p < 0.05). By contrast, the hearts from young and old females exhibited a similar post-ischemic functional recovery and no age-dependent difference in infarcts. There was a sex difference in the young group, where ventricular function (LVDP, +dP/dt, -dP/dt) recovered better and infarcts were smaller in females than males. Estradiol levels were highest in young females. Testosterone was high in young males but low in females and old males, which suggested beneficial effects of low testosterone. Indeed, the hearts from GDX males exhibited much better recovery of LVDP in reperfusion than that from intact males (values were 64.4 ± 7.5 % vs. 21.8 ± 9.2%; p < 0.05). The GDX hearts also had smaller infarcts than the hearts from intact males (p < 0.05).ConclusionsAlthough age had no effect on susceptibility to I/R injury after cardioplegic arrest in females, it actually protected against injury in older males. Our findings indicate that low testosterone may be protective against I/R injury following cardioplegic arrest in older males.

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Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity.

Publications

Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity.

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