Neutrophil activation following TDI bronchial challenges to the airway secretion from subjects with TDI‐induced asthma

Abstract

SummaryBackground The immunopathological mechanism for occupational asthma induced by toluene diisocyanate (TDI) remains to be further clari®ed. There have been few reports suggesting involvement of neutrophils in inducing bronchoconstriction after TDI inhalation. Objectives To further understand the role of neutrophils in the pathogenesis of TDIinduced asthma. Materials and methods Eight TDI-induced asthmatic subjects were classi®ed as group I, and ®ve exposed workers who had complained of work-related symptoms and worked in the same workplace, but showed negative bronchial challenges were enrolled as controls (group II). Serum neutrophil chemotactic activity during TDI bronchial challenge test was measured by the Boyden chamber method. Induced sputum was collected before and after the TDI bronchial challenge test. The myeloperoxidase (MPO) and interleukin (IL) -8 levels in the sputum were measured using RIA and ELISA. Result Serum neutrophil chemotactic activity signi®cantly increased at 10 min (P 0.01), then decreased at 60 min (P 0.02) and remained unchanged for up to 420 min (P 0.07) in group I subjects, while no signi®cant changes were found in group II subjects (P > 0.05). MPO and IL-8 were abundantly present in the sputum of all the TDI-induced asthmatic subjects and they increased signi®cantly at 420 min after the bronchial challenges (P 0.02, P 0.03, respectively), while no signi®cant changes were noted in group II subjects (P > 0.05). Conclusion These ®ndings support the view that activated neutrophils may contribute to bronchoconstriction induced by TDI which may be associated with IL-8 release.

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

“…Its levels are commonly increased in neutrophilic asthma and TDI-OA [9]. Although no significant increases in IL-8 after MDI exposure were noted in the airway secretions of MDI-OA patients in the present study, sputum IL-8 levels were highly correlated with sputum eosinophil counts and ECP levels, which may contribute to eosinophilic activation.…”

“…In our previous study, serum-specific IgE and IgG antibodies were shown to be increased in some MDI-induced occupational asthma (MDI-OA) patients, of which specific IgG antibodies were more associated with work-related respiratory symptoms (WRRS) [7]. Activated neutrophils have also been suggested to play a role in the pathogenic mechanisms of toluene diisocyanate-induced occupational asthma (TDI-OA) [8,9]. However, these cellular mechanisms involved have not been investigated in MDI-OA.…”

A murine model of toluene diisocyanate–induced asthma can be treated with matrix metalloproteinase inhibitor

“…22,23 Sustained release of these inflammatory products enhances neutrophil-induced inflammation in the airway and subsequent airway hyperreactivity. 24,25 As we previously reported, 20 neutrophils may contribute to bronchoconstriction induced by TDI. Furthermore, the number of eosinophils in the BAL fluid increased in our TDIinduced asthma model, although the magnitude was less than that seen with neutrophils.…”

“…3,4,20 In TDI-induced asthma in human subjects, neutrophilia in BAL fluid has been found in association with asthmatic reactions induced by isocyanate challenge. 21 Neutrophils could be an important source of proinflammatory cytokines and proteolytic enzymes.…”

Genetic markers for occupational asthma

“…5 As in other forms of asthma, inflammatory changes are found in the airways of patients with TDI asthma, along with eosinophils, T cells, and collagen deposition as well as the typical range of cytokines associated with asthma. [6][7][8] When T-cell clones were derived from the airways of patients with TDI asthma, the majority were CD8 + and expressed IL-5 and IFN-γ, 9 suggesting similarities with the T-cell response seen in patients with atopic asthma. 10 However, when patients with TDI asthma underwent bronchial challenge, they showed a more marked neutrophil response 8 than would be expected in corresponding pollen or house dust mite challenges.…”