The prevalence studies on specific IgE to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate in TDI-induced asthma have shown variable results. In this study, we attempted to compare specific IgE bindings to TDI-HSA conjugate and its specificity using 3 different conjugates. Sera were collected from 20 TDI-induced asthma and 10 controls. Specific IgE were measured by ELISA using three TDI-HSA conjugates; two from Carnegie Mellon (CM; 98 and 99 CM conjugates) and one from Ajou University. To evaluate specificity and cross-reactivity, ELISA inhibition tests were applied. Positive and negative predictive values between Ajou conjugate and 98 CM conjugate were 75% and 100%. Those between Ajou and 99 CM were 100% and 93.8%. One patient showed an isolated positive response to the Ajou with negative responses to the other two conjugates. ELISA inhibition test using this patient's serum revealed the significant inhibitions by the Ajou and minimal inhibitions by the others. On the other hand, another patient showed an isolated positive response to 99 CM with negative responses to the others, and ELISA inhibition test showed significant inhibition by 99 CM with minimal inhibitions by the others. These results suggest that specific IgE bindings to a new antigenic determinant of TDI-HSA conjugate can be heterogeneous and differ from one individual to another.
Asthma/immunology ; Asthma/chemically induced* ; Enzyme-Linked Immunosorbent Assay ; Human ; IgE/biosynthesis* ; Serum Albumin/immunology* ; Toluene 2,4-Diisocyanate/immunology* ; Toluene 2,4-Diisocyanate/adverse effects

Isocyanate is the most prevalent agent in occupational asthma(OA) in Korea. We analyzed 43 toluene diisocyanate(TDI) induced OA patients of whom 81% were found to be spray painters. The bronchial sensitivity of all subjects was confirmed by TDI-bronchial challenge test. Serum-specific IgE antibodies to isocyanate-human serum albumin(HSA) conjugate were detected by RAST technique(Pharmacia, Sweden). Bronchial challenge test results revealed 21(57%) early, 5 late only, 4 dual, and 12 atypical responders(5 prolonged immediate, 6 square-shaped, 1 progressive). Four(9%) subjects had negative results on the methacholine bronchial challenge test. High levels of serum specific IgE antibody to isocyanate-HSA were found in 17(40%) patients. The prevalence of a specific IgE antibody was not associated with a type of TDI-bronchial challenge test response, smoking and atopic status, presence of rhino-sinusitis and systemic symptoms, or a degree of airway hyperresponsiveness to methacholine(p> 0.05). The period of latency, ranging from 3 to 132 months, was significantly longer in high specific IgE responders (p< 0.05). These data suggest that 40% of isocyanate-induced occupational asthma patients had high specific IgE antibody to isocyanate-HSA conjugate. The presence of specific IgE antibody does not seem to correlate with clinical parameters.
Allergens/adverse effects/*immunology ; Asthma/chemically induced/*immunology ; Female ; Human ; Immunoglobulin E/blood/*immunology ; Male ; Occupational Exposure/*adverse effects ; Toluene 2,4-Diisocyanate/adverse effects/*immunology

Isocyanates are the most significant cause of occupational asthma in our country. To evaluate the prevalence of work-related respiratory symptoms and immunologic sensitization to it, we performed a questionnaire survey, allergy skin test, radioallergosorbent test (RAST) to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate and methacholine bronchial challenge test on 23 isocyanate-exposed employees and 9 unexposed controls working in a zipper factory. Six employees (26.1%) complained of work-related respiratory symptoms and three symptomatic workers showed significant bronchoconstrictions on TDI-bronchoprovocation test. Three (13%) asymptomatic workers had high specific IgE antibodies to TDI-HSA and none of the TDI-sensitive asthmatic workers had specific IgE antibody. One of the TDI-sensitive asthmatic workers showed a negative result on the initial methacholine bronchial challenge test, but bronchial hyperresponsiveness developed after the TDI challenge. It was suggested that TDI-sensitive asthma was noted in three (13%) of 23 exposed workers and that asymptomatic workers could have high specific IgE antibody. Measurement of the changes in bronchial hyperresponsiveness after the TDI challenge could be helpful to diagnose TDI-sensitive asthma.
Adult ; Asthma/*chemically induced/diagnosis ; Bronchial Provocation Tests ; Humans ; Immunoglobulin E/analysis ; Occupational Diseases/*chemically induced/diagnosis ; Occupational Exposure ; Serum Albumin/immunology ; Toluene 2,4-Diisocyanate/*adverse effects/immunology

BACKGROUND: An appreciable number of patients with toluene diisocyanate (TDI)-induced asthma have high serum levels of specific IgE (sIgE) antibody to TDI-human serum albumin conjugate (HSA). A recent investigation suggested a role of specific IgG (sIgG) in the development of TDI asthma. METHODS: We observed the changes in the levels of specific IgE and IgG antibodies to TDIHSA conjugate in TDI-induced asthmatic patients during seven years avoidance. RESULTS: Six subjects with high sIgE and five with high sIgG were enrolled. All of them had taken anti-asthmatic medications with complete avoidance. Serum levels of sIgE and sIgG to TDI-HSA conjugate were detected by ELISA. The level of sIgE continued to decline up to 7 years and the mean half-life was 3.9 years. The mean half-life of sIgG was 4.5 yrs. CONCLUSION: These findings suggest that both sIgE and sIgG to TDI-HSA conjugate may persist for several years after the last exposure to TDI.
Adult ; Asthma/*chemically induced/immunology ; Biological Markers/blood ; Human ; Immunoglobulin E/blood/*immunology ; Immunoglobulin G/blood/*immunology ; Longitudinal Studies ; Male ; Middle Aged ; Serum Albumin/*immunology ; Support, Non-U.S. Gov't ; Toluene 2,4-Diisocyanate/adverse effects/*immunology

This investigation was designed to confirm IL-8 production from human bronchial epithelial cells with toluene diisocyanate (TDI) exposure and to examine the effects of pro-inflammatory cytokine and dexamethasone. We cultured Beas-2B, a bronchial epithelial cell line with TDI-HSA conjugate and compared with those without conjugate. IL-8 in the supernatant was measured by ELISA. To evaluate the effect of proinflammatory cytokines, peripheral blood mononuclear cells (PBMC) were collected from TDI- and non-TDI asthma patients, and were added to the epithelial cell culture. Dexamethasone or antibodies to TNF-alpha and IL-1beta were pre-incubated with PBMC supernatant. There was a significant production of IL-8 from bronchial epithelial cells with addition of TDI-HSA conjugate in a dose-dependent manner, which was significantly augmented with addition of PBMC supernatant. Higher production of IL-8 was noted with addition of PBMC supernatant from TDI-asthma patients than in those from non-TDI asthma patients. IL-1beta and IL-1beta/TFNalpha antibodies were able to suppress the IL-8 productions. Pre-treatment of dexamethasone induced dose-dependent inhibition of the IL-8 production. These results suggest that the IL-8 production from bronchial epithelial cells contribute to neutrophil recruitment occurring in TDIinduced airway inflammation. IL-1beta released from PBMC of TDI-induced asthma patients may be one of the pro-inflammatory cytokines to enhance IL-8 production.
Asthma/immunology ; Bronchi/*cytology/metabolism ; Cell Line ; Dexamethasone/pharmacology ; Epithelial Cells/cytology/*drug effects/*metabolism ; Glucocorticoids/pharmacology ; Human ; Interleukin-8/*metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Support, Non-U.S. Gov't ; Toluene 2,4-Diisocyanate/*toxicity

OBJECTIVES: We established a Wistar rat model of asthma caused by toluene diisocyanate (TDI) exposure, and investigated the relationship between TDI exposure concentrations and respiratory hypersensitivity, airway inflammation, and cytokine secretions in animals, to better understand the mechanism of TDI induced occupational asthma. METHODS: Wistar rats were exposed to two different concentrations of TDI vapor four hours a day for five consecutive days. Bronchoalveolar lavage (BAL) was performed, and differential leucocytes from the BAL fluid were analyzed. Lung histopathological examination was carried out to investigate the inflammatory status in the airways. Production of cytokines interleukin (IL)-4 and IL-5 productions in the BAL fluid in vivo was determined with enzyme-linked immunosorbent assay kits. RESULTS: The TDI-exposed rats exhibited greater airway hypersensitivity symptoms than the control rats. The BAL differential cell count and lung histopathological examination demonstrated that inflammation reactions were present in both the central and peripheral airways, characterized with marked infiltration of eosinophils in the TDI-exposed rats. The cytokine assay showed that IL-4 and IL-5 were predominantly produced in the BAL fluid in vivo. CONCLUSIONS: These findings imply that TDI exposure concentrations may greatly affect the occurrence and extent of inflammatory events and that Th2 type cytokines may play an important role in the immunopathogenesis of TDI-induced occupational respiratory hypersensitivity.
Animals ; Bronchoalveolar Lavage Fluid/chemistry/cytology ; Enzyme-Linked Immunosorbent Assay ; Eosinophils/cytology/immunology ; Female ; Gases/chemistry ; Hypersensitivity/pathology ; Interleukin-4/*analysis ; Interleukin-5/*analysis ; Lung/*drug effects/pathology/secretion ; Rats ; Rats, Wistar ; Toluene 2,4-Diisocyanate/*toxicity

To evaluate the clinical significance of autoantibodies to three major epithelial cytokeratins (CK) -- CK8, CK18, and CK19 -- we compared 66 patients with toluene diisocyanate (TDI)-induced asthma (group I) with three control groups: 169 asymptomatic exposed subjects (group II), 64 patients with allergic asthma (group III), and 123 unexposed healthy subjects (group IV). Serum IgG, specific for human recombinant CKs, were measured by ELISA (enzyme linked immunosorbent assay), and ELISA inhibition tests were performed. The existence of these antibodies was confirmed by IgG immunoblot analysis. Anti-TDI-HSA (human serum albumin) IgE and IgG antibodies were measured by ELISA in the same set of the patients. The prevalence of CK8, CK18, and CK19 auotantibodies in group I was significantly higher than in the other three groups. Results of the ELISA inhibition test showed significant inhibition with the addition of three CKs in a dose-dependent manner. No significant association was found between CK autoantibodies and the prevalence of anti- TDI-HSA IgG and IgE antibodies. These results suggest that autoantibodies to CK18 and CK19 can be used as serologic markers for identifying patients with TDI-induced asthma among exposed workers.
Toluene 2,4-Diisocyanate/*toxicity ; Sensitivity and Specificity ; Occupational Diseases/chemically induced/*diagnosis ; Middle Aged ; Male ; Keratins/*immunology ; Keratin-8/immunology ; Keratin-19/immunology ; Keratin-18/immunology ; Immunoblotting ; Humans ; Female ; Enzyme-Linked Immunosorbent Assay ; Biological Markers/blood ; Autoantibodies/*blood ; Asthma/chemically induced/*diagnosis ; Adult

BACKGROUND: Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring. METHODS: Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays. RESULTS: We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 μg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 μg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 μg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 μg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively). CONCLUSION The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.
Adult ; Air Pollutants, Occupational ; adverse effects ; immunology ; Environmental Monitoring ; Humans ; Immunoglobulin G ; blood ; immunology ; Japan ; Male ; Manufacturing and Industrial Facilities ; statistics & numerical data ; Middle Aged ; Occupational Diseases ; blood ; chemically induced ; Occupational Exposure ; adverse effects ; statistics & numerical data ; Phthalic Anhydrides ; immunology ; toxicity ; Respiratory Hypersensitivity ; blood ; chemically induced ; Toluene 2,4-Diisocyanate ; immunology ; toxicity ; Workforce

OBJECTIVETo investigate the effect and mechanism of BSDW on the model of allergic rhinitis and the model of guinea pigs by histamine shocking in guinea pigs.

METHODUsing the model of allergic rhinitis in guinea pigs caused by 10% TDI, we observed the effect of BSDW on physiological and pathological symptoms of allergic rhinitis in guinea pigs, the effect of the levels of serum IgE and serum and nasal histamine. Using the model of guinea pigs by histamine shocking, we observed the effect of BSDW on physiological symptoms in guinea pigs.

RESULTBSDW significantly relieved the pathological symptoms of allergic rhinitis in guinea pigs, alleviated the hyperplasia of columnar epithelium, decreased the number of monocyte and eosinocyte compared with the model group. It also reduced the levels of serum IgE, and decreased the release of serum and nasal histamine. BSDW significantly prolonged the occurent time of gasping, eclampsia and death caused by shock, reduced the times of gasping in the model of guinea pigs by histamine shocking.

CONCLUSIONBSDW has significant effect against allergy. The mechanism relates to its effects of decreasing the levels of serum IgE and inhibiting the release of serum and nasal histamine.

Administration, Intranasal ; Animals ; Anti-Allergic Agents ; pharmacology ; Asarum ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Female ; Guinea Pigs ; Histamine ; blood ; Immunoglobulin E ; blood ; Lamiaceae ; chemistry ; Male ; Nasal Mucosa ; immunology ; Plants, Medicinal ; chemistry ; Rhinitis, Allergic, Perennial ; immunology ; Scutellaria ; chemistry ; Toluene 2,4-Diisocyanate