Airway Inflammation and Bronchial Remodelling in Toluene Diisocyanate‐exposed BALB/c Mouse Model

Abstract

Toluene diisocyanate (TDI), a highly reactive industrial chemical, is one of the leading causes of occupation‐related asthma in industrialized countries. The pathogenesis of TDI‐induced asthma, however, remains not fully understood, in part due to lack of appropriate animal models. Twenty five female BALB/c mice (age: 8 weeks) were randomly divided into 5 groups: Ovabumin (OVA); OVA peptide amino acid residues No. 323–339 (Pep); TDI; alum and physiological saline. Mice were intraperitoneally injected with 25 μg OVA or pep absorbed on 300 μg alum, 300 μg alum or saline on days 0, 7 and 14. For the TDI group, mice were sensitized subcutaneously with 20 μl neat TDI on day 0; 20 μl of TDI in olive oil (1:10) on days 7 and 14; on days 21–23. Then each group was challenged intranasally with 20 μl of 1% OVA, 1% Pep, 1% TDI, 10% alum and saline respectively. On day 28, mice were killed under pentothal anesthesia. The results demonstrated that neutrophil‐dominant inflammation with a few eosinophil infiltration occurred in the peri‐bronchial and peri‐vascular regions of the lungs. This was accompanied by hyperplasia/hypertrophy of cells lining the airways and mucus production as shown by HE staining. Positive immunohistochemical MBP staining in parenchyma was also shown. Th2 cytokine IL‐4 and IgE production were significant increased 5 days after last challenge while IFN‐γ level was below the detection limit. Conclusion: the clear elevation of IL‐4 and IgE could allow to conclude a possible Th2‐like dominated allergic response in TDI‐exposed BALB/c mouse model.

Histamine Release and Inflammatory Cell Infiltration in Airway Mucosa in Methylene Diphenyl Diisocyanate (MDI)-Induced Occupational Asthma

“…Mast cells [19], activated T cells, and levels of neutrophilic infiltration [20] are also increased in TDI-OA as compared with AEC and AA. These results have been replicated in animal models of TDI-OA [21,22]. Although Bentley et al [23] reported that activated T cells and eosinophils were Fig.…”

Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats

“…The increased neutrophils should be responsible for the cell recruitment in lung. However, fewer neutrophils and eosinophils infiltration were observed in saline and control animals around the airways (Sun et al, 2007).…”

Safe exposure level for diacetyl

“…8 Isocyanates have been found to generate a similar immune response. 9 Thus, whatever the 'chemical reaction,' diacetyl and isocyanates appear to act through at a similar immune mechanism.…”