Airway inflammation and bronchial remodelling in toluene diisocyanate-exposed BALB/c mouse model.
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 microg OVA or pep absorbed on 300 microg alum, 300 microg alum or saline on days 0, 7 and 14. For the TDI group, mice were sensitized subcutaneously with 20 microl neat TDI on day 0; 20 microl of TDI in olive oil (1:10) on days 7 and 14; on days 21-23. Then each group was challenged intranasally with 20 microl 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-gamma level was below the detection limit.


CONCLUSIONS
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.
Sun
L-Z
LZ
Allergy Research Group, Laboratory of Clinical Biochemistry and Institute of Medicine, Haukeland University Hospital and University of Bergen, Bergen, Norway.
Elsayed
S
S
Bronstad
A M
AM
Van Do
T
T
Irgens
A
A
Aardal
N P
NP
Aasen
T B
TB
D000534:Alum Compounds / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D015847:Interleukin-4 / Q000032:analysis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
D000534:Alum Compounds; D016207:Cytokines; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4; C041524:aluminum sulfate; D007073:Immunoglobulin E; D010047:Ovalbumin