Differential effects of formaldehyde exposure on airway inflammation and bronchial hyperresponsiveness in BALB/c and C57BL/6 mice

Abstract

Epidemiological evidence suggests that formaldehyde (FA) exposure may influence the prevalence and severity of allergic asthma. However, the role of genetic background in FA-induced asthma-like responses is poorly understood. In the present study, we investigated the nature and severity of asthma-like responses triggered by exposure to different doses of FA together with or without ovalbumin (OVA) in two genetically different mouse strains-BALB/c and C57BL/6. Both mouse strains were divided into two main groups: the non-sensitized group and the OVA-sensitized group. All the groups were exposed to 0, 0.5 or 3.0 mg/m3 FA for 6 h/day over 25 consecutive days. At 24 h after the final FA exposure, the pulmonary parameters were evaluated. We found that FA exposure induced Th2-type allergic responses in non-sensitized BALB/c and C57BL/6 mice. In addition, FA-induced allergic responses were significantly more prominent in BALB/c mice than in C57BL/6 mice. In sensitized BALB/c mice, however, FA exposure suppressed the development of OVA-induced allergic responses. Exposure to 3.0 mg/m3 FA in sensitized C57BL/6 mice also led to suppressed allergic responses, whereas exposure to 0.5 mg/m3 FA resulted in exacerbated allergic responses to OVA. Our findings suggest that FA exposure can induce differential airway inflammation and bronchial hyperresponsiveness in BALB/c and C57BL/6 mice.

Fig 1. Experimental protocols for exposure of BALB/c and C57BL/6 mice to different doses of FA with or without OVA sensitization.

In the sensitized group (D, E and F), mice were intraperitoneally injected with 50 μg OVA plus 1.75 mg aluminum hydroxide on days 1, 7 and 14 during the exposure period. The 1% aerosolized OVA challenge was carried out on days 19–25. In the non-sensitized group (A, B and C), mice were sham sensitized by 0.9% saline injections and challenged with 0.9% saline aerosols following the same protocols. Both the non-sensitized and sensitized mice were exposed to three concentrations of FA (0, 0.5 and 3.0 mg/m³) for 6 h/day over 25 consecutive days. All data shown are representative of two separate experiments.

Fig 2. Effect of FA exposure on cytokine production in the BALF from BALB/c and C57BL/6 mice with or without OVA sensitization.

At 24 h after the final FA exposure, the BALF was collected from all groups of mice, and the concentrations of IL-4, IL-5, IL-13 and IFN-γ were measured by ELISA. (A) Effect of FA exposure on cytokine production in the non-sensitized and sensitized BALB/c (□) and C57BL/6 (■) mice. (B) Comparison of the effect of inhaled FA dose on cytokine production between BALB/c (□) and C57BL/6 (■) mice. (C) Differences in cytokine production after sensitization with OVA in BALB/c (□) and C57BL/6 (■) mice. Data are presented as the mean± SE (n = 8 mice/group) (* p < 0.05).

Fig 3. Effect of FA exposure on airway inflammation in BALB/c and C57BL/6 mice with or without OVA sensitization.

Airway inflammation was assessed using inflammatory cell counts in the BALF. (A) Effect of FA exposure on inflammatory cell counts in the non-sensitized and sensitized BALB/c (□) and C57BL/6 (■) mice. (B) Comparison of the effect of inhaled FA dose on eosinophil counts between BALB/c (□) and C57BL/6 (■) mice. (C) Differences in eosinophil counts after sensitization with OVA in BALB/c (□) and C57BL/6 (■) mice. Data are presented as the mean± SE (n = 8 mice/group) (* p < 0.05).

Fig 4. Effect of FA exposure on bronchial responsiveness to methacholine in BALB/c and C57BL/6 mice with or without OVA sensitization.

Inspiratory resistance (Ri) and expiratory resistance (Re) were recorded to determine the bronchial responsiveness to methacholine. (A) Effect of inhaled FA dose on inspiratory resistance (Ri) in the non-sensitized and sensitized BALB/c and C57BL/6 mice. (B) Effect of inhaled FA dose on expiratory resistance (Re) in the non-sensitized and sensitized BALB/c and C57BL/6 mice. Data are presented as the mean± SE (n = 6 mice/group). * p < 0.05 compared with the naïve group. # p < 0.05 compared with the OVA group. ** p < 0.05 for the 0.5 FA group compared with the 3.0 FA group. (C) Comparison of the increases of Ri and Re after FA exposure between BALB/c and C57BL/6 mice. Data are expressed as % maximal increases over naïve controls (mean± SE) (* p < 0.05).

Fig 5. Effect of FA exposure on serum OVA-specific immunoglobulin in BALB/c and C57BL/6 mice.

At 24 h after the final FA exposure, blood samples were collected from BALB/c (□) and C57BL/6 (■) mice, the concentrations of OVA-specific IgE, IgG1 and IgG2a in the sera were measured by ELISA. Data are presented as the mean± SE (n = 8 mice/group) (* p < 0.05).