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

• Published in: Cellular immunology 2019-11, Vol.345, p.103988-103988, Article 103988
• Main Authors: vom Steeg, Landon G., Attreed, Sarah E., Zirkin, Barry, Klein, Sabra L.
• Format: Article
• Language: English
• Subjects: 2009 H1N1; Age Factors; Aging; Androgens; Androgens - pharmacology; Animals; CD8+ T cells; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cytokines - blood; Cytokines - immunology; Cytokines - metabolism; Female; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - physiology; Lung - drug effects; Lung - immunology; Lung - virology; Male; Mice, Inbred C57BL; Orthomyxoviridae Infections - drug therapy; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Resistance; Severity of Illness Index; Sex Factors; Testosterone - pharmacology; Tolerance
• ISSN: 0008-8749; 1090-2163; 1090-2163
• DOI: 10.1016/j.cellimm.2019.103988

•Aged male mice clear influenza A virus (IAV) slower and experience greater morbidity and mortality than adult males.•As compared with adult males, aged males experience pulmonary cytokine dysregulation and delayed influx and contraction of IAV-specific CD8+ T cells in the lungs.•Testosterone treatment of aged males improves pulmonary cytokine responses, but has no effect on the age-associated delayed clearance of virus or dysregulation of virus-specific CD8+ T cells in the lungs of male mice. 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.