Gender comparison in a murine model of allergen-driven airway inflammation and the response to budesonide treatment

Abstract

Background: Evidence suggests that gender differences exist in the severity of many immunological diseases and their response to glucocorticosteroid treatment. In this report, we have used a murine model of ovalbumin-induced lung inflammation to address whether gender could affect the systemic response, airway inflammation and hyperreactivity and their responses to budesonide.

Results: Following an acute ovalbumin challenge, actively sensitised BALB/c mice developed a time-dependent increase in interleukin-4 and interleukin-5 production and inflammatory cell influx into bronchoalveolar lavage fluid. Apart from an increased number of lymphocytes in female mice at day 3 post-challenge, none of the above parameters were affected by gender. Blood leukocyte numbers were also unaffected, whereas a two-fold increase in total serum immunoglobulin E was observed in female mice. Budesonide, given intranasally, did not affect the blood parameters, but dose-dependently inhibited the pulmonary inflammation and airway hyperreactivity in both male and female mice. Female mice were slightly less sensitive to budesonide's inhibitory action on interleukin-5 production and the development of airway hyperreactivity.

Conclusions: Our results suggest that, apart from a 2-fold increase in serum immunoglobulin E levels observed in female mice, gender is not a major factor in the present murine model of ovalbumin-induced lung inflammation. In contrast, gender might slightly influence the potency of test compounds such as steroids.

Figure 1

Time course of bronchoalveolar lavage inflammatory cell infiltration and interleukin-4 and interleukin-5 levels following ovalbumin challenge. Actively sensitised female and male mice were challenged with a nebulised solution of ovalbumin and sacrificed at different time points for bronchoalveolar lavage. Data are expressed as mean ± standard error of 6–8 mice per group. # indicates significance when comparing male and female mice at the same time point.

Figure 2

Effect of budesonide treatment on bronchoalveolar lavage inflammatory cell infiltration and interleukin-5 and interleukin-4 levels at day 1 post challenge. Actively sensitised female and male mice were treated intranasally with vehicle (n = 10), 0.3 mg/kg (n = 10) or 3 mg/kg (n = 10) of budesonide and challenged with ovalbumin 1 hour later. Data are expressed as mean ± standard error. * and # indicate significance against the vehicle-treated group and when comparing male and female mice, respectively.

Figure 3

Effect of budesonide treatment on bronchoalveolar lavage inflammatory cell infiltration at day 2 post challenge. Actively sensitised female and male mice were treated intranasally with vehicle (n = 8), 0.3 mg/kg (n = 8) or 3 mg/kg (n = 8) of budesonide and challenged with ovalbumin 1 hour later. Data are expressed as mean ± standard error. * and # indicate significance against the vehicle-treated group and when comparing male and female mice, respectively.

Figure 4

Measurement of airway hyperreactivity to aerosolised methacholine and effect of budesonide treatment. Actively sensitised female and male mice were treated intranasally with vehicle and challenged with PBS (n = 8) or ovalbumin (n = 10) one hour later. Different groups of animals were intranasally treated with 0.3 mg/kg (n = 10) or 3 mg/kg (n = 10) of budesonide and challenged with ovalbumin one hour after. Airway hyperreactivity to aerosolised methacholine was measured 24 hours after the challenge using whole body plesthysmography. ED₃₀₀ values for methacholine (panel B) were calculated from the dose-response display in panel A by log-linear interpolation. Data are expressed as mean ± standard error. * and # indicate significance against the vehicle-treated group and when comparing male and female mice, respectively.