Influence of gender and interleukin-10 deficiency on the inflammatory response during lung infection with Pseudomonas aeruginosa in mice

Abstract

Cystic fibrosis females have a worse prognosis compared to male patients. Furthermore, cystic fibrosis patients infected with Pseudomonas aeruginosa have been shown to have dysregulated cytokine profiles, as higher levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-8, and lower levels of IL-10 are found in the bronchoalveolar lavage fluid compared to healthy controls. The present study was aimed at investigating the importance of gender and IL-10 in the susceptibility of C57BL/6 mice to pulmonary infection with Pseudomonas aeruginosa. We found that wildtype females were more susceptible than males to infection, as we observed greater weight loss, higher bacterial load, and inflammatory mediators in their lungs. IL-10 knockout mice, both females and males, had higher levels of TNF-alpha in the lungs compared to wildtype mice and maintained higher levels of polymorphonuclear cells and lower levels of macrophages for a longer period of time. Our results demonstrate that the number of bacteria recovered from the lungs of IL-10 knockout male mice was significantly higher than that observed in their wildtype male counterparts and we show that neutralization of IL-10 in infected female mice for a prolonged period of time leads to increased susceptibility to infection. Results reported in this study clearly demonstrate that females, both wildtype and IL-10 knockout mice are more susceptible to Pseudomonas aeruginosa infection than males, and that they mount a stronger inflammatory response in the lungs.

Figure 1

Alveolar inflammatory cells in the lungs of P. aeruginosa infected mice. The number of alveolar cells from the BALF was evaluated in IL-10 KO (open) and WT (solid) male (a) and female (b) mice 4 days postinfection. Data are presented as individual values of seven to 10 mice and the horizontal line represents the median. Significant (*) difference was found between IL-10 KO and WT males (P ≤ 0·001). These results illustrate three independent experiments performed under the same conditions.

Figure 2

Bacterial burden in the lungs of P. aeruginosa infected mice. The CFU counts were assessed in the lung tissue homogenates (a) and BALF (b) of IL-10 KO (open) and WT (solid) mice 4 days postinfection. Data are presented as individual values of seven to 10 mice and the horizontal line represents the median. Significant (*) differences were found between IL-10 KO and WT males in the CFU counts in lung tissue homogenates (P = 0·021), and BALF (P = 0·021). These results illustrate three independent experiments performed under the same conditions.