Impact of Age of Infection and Sex on the Physiological Consequences of Influenza A Infection

Background: Murine models have been extensively used to study lung development and physiology. It is apparent that there is sexual dimorphism in various aspects of these processes. Furthermore, sex differences in immune function are well established in both animals and humans, with males typically displaying weaker humoral and cell−mediated immune responses, with females often exhibiting higher Th2 responses.

Methods: We inoculated male and female weanling (3 wks old) and adult (8 wks old) BALB/c mice with influenza A and measured lung function, hyperresponsiveness to methacholine (Mch) and inflammatory responses during the acute infectious stage (day 4) and after recovery (day 21). Results: During the acute infectious stage, there were significant effects of influenza infection on airway resistance (Raw), tissue damping (G), tissue elastance (H) and number/type of inflammatory cells in the bronchoalveolar lavage (BAL) for both males and females of both ages when compared to media controls. Greater responses were seen in adult females than in adult males (e.g. G: p = 0.020; H: p =0.016; macrophages: p = 0.003; neutrophils: p = 0.003), and in weanling females compared to weanling males, especially in the lung parenchyma. Most parameters had returned to baseline levels 21 days after influenza inoculation in both age groups and sexes.

Conclusions: We've shown increased lung hyperresponsiveness and inflammatory responses in female mice exposed to influenza A compared to male mice. These results are contrary to most previous research, which indicate that males are generally more susceptible to respiratory viral infections. Possible explanations for this include testosterone levels or higher Th2 responses of females, which may inhibit their Th1 based response to viral infection.