New Clues to Why Influenza Illness Is More Severe in Women than Men

NIAID Now | January 25, 2019

Differences in disease severity between females and males have been described for several pulmonary (lung) infections, including influenza (flu). In influenza infections, studies have shown that females have more inflammation in the lungs and overall have a more severe outcome compared to males, despite having comparable levels of flu virus in the body. This suggests that the worse outcome in females may result from an inability to resolve inflammation rather than a failure in controlling viral replication.

To help understand the disparate outcomes between males and females following influenza infection, NIAID-funded researchers looked for possible sex-based differences in production of a growth factor called amphiregulin (AREG). This growth factor helps control tissue repair of membranes that line body cavities, such as in the respiratory tract. In response to damage from inflammation, cells that line the nasal cavities and airways release AREG and other factors that help repair and restore the integrity of tissues damaged during infection.

The researchers found that AREG production was greater in lung tissue and laboratory-grown cells derived from males (both human and mouse) than from females. They further showed that this difference, along with the presence of the male sex hormone testosterone, contributed to the faster recovery of males as compared to females following influenza infection. This finding suggests that AREG and testosterone both contribute to limiting tissue damage from inflammation and mediate faster repair of damaged lung tissue.

Results from this study contribute to our understanding of the differences between males and females following influenza infection. Damage from inflammation contributes to more severe outcomes in several types of infection, including HIV, influenza, and Staphylococcus aureus. This study suggests that males may better tolerate influenza infections and have improved repair and recovery of damaged tissue, and that this sex-based difference is mediated by elevated levels of both AREG and testosterone, either independently or in combination.

Reference: Vermillion MS et al. Production of amphiregulin and recovery from influenza is greater in males than females. Biology of Sex Differences. 2018 July 17; 9(1):24.

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