IL-4 and IL-5 Secretions Predominate in the Airways of Wistar Rats Exposed to Toluene Diisocyanate Vapor / 예방의학회지

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.

Clinical and Immunological Responses in Ocular Demodecosis

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1beta, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1beta in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1beta and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.

The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice

CpG-Oligodeoxynucleotide (ODN) has two backbones. Phosphorothioate backbone (PS) shows a strong immunostimulating effect while phosphodiester (PE) shows little in vivo. 3' hexameric deoxyriboguanosine-run (3' dG6-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulation and to protect against asthma when injected at the time of sensitization in mice. We evaluated the treatment effects of PE and PS CpG-ODN with or without 3' dG6-run on asthma in presensitized mice. BALB/c mice sensitized with ovalbumin and alum were challenged with 1% ovalbumin on three days. CpG-ODNs (100 microgram) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG6: CpG-ODN with 3' dG6-run, PE*-CpG-dG6: PE-CpG-dG6 with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG6 only increased ovalbumin-specific IgG2a. PE*-CpG-dG6 increased ovalbumin-specific IgG2a but also reduced BAL fluid eosinophils and airway hyperresponsiveness. PS-CpG increased ovalbumin-specific IgG2a, reduced airway inflammation and airway hyperresponsiveness. PS-CpG-dG6 was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG6-run but also the modification of two PS linkages at 5' terminus to inhibit features of asthma. PS-CpG was strong enough to inhibit asthma but PS-CpG-dG6 was less effective.

Expression of cytokines and monosaccharide transporters in the duodenal mucosa of patients with gastrointestinal symptoms in rural Thailand.

Levels of cytokines and GLUT family monosaccharide transporters in the duodenal mucosa were examined in patients from Nong Khai, Thailand, who had underwent gastroscopy because of gastrointestinal problems. Duodenal biopsy specimens were collected from a total of 33 patients (24 males and 9 females, 45.0 +/- 13.5 years old). Ten patients had present or recent intestinal helminth infections, including strongyloidiasis, taeniasis or ascariasis (group A), 7 were urease-test positive, indicating Helicobacter pylori infection (group B), and 16 had neither helminth infections nor urea-test positivity (group C). Total RNA was extracted from the biopsied specimens and a semi-quantitative RT-PCR was performed. The positivities for IL-13, IL-5 and IFN-gamma mRNA expressions in the patients were 24.2, 60.6 and 100%, respectively, with the highest IL-13 and IL-5 positivities in group A, followed by group C and B. The IL-5 positive rate was significantly higher among patients with high peripheral blood eosinophil counts (> 4%) than in patients with low peripheral blood eosinophil counts. GLUT-1 and GLUT-5 were detectable in all the patients. Although GLUT-1 expressions did not differ among groups A, B and C. GLUT-5 expressions were significantly lower in group B than in group C. These results indicate that helminth and H. pylori infections result in different immunopathological responses in the duodenal mucosa, lower expressions of type 2 cytokines and monosaccharide transporters in H. pylori infections than in helminth infections.

Citoquinas inducidas por la inmunización experimental antitetánica. Efecto de la formulación vacunal / [Cytokines induced by experimental anti-tetanus immunization. Vaccine formulation effect]

Several factors are involved in the selective activation of T helper 1 or T helper 2 cells, such as the type of antigen-presenting cells involved in the immune response and the different physical characteristics of antigens. The aim of this work was to evaluate if adding other antigens to tetanus toxoid modifies the original immune response. BALB/c mice were immunized with tetanus and diphtheria toxoids associated with whole-cell Bordetella pertussis (DTPw vaccine), B. pertussis soluble antigens (DTPa vaccine) or Salmonella typhi plus DTPa (DTPaSt vaccine). DTPw and DTPaSt immunization induced a T helper 1/T helper 2 (Th1/Th2) anti-tetanus response with gamma interferon and interleukin 5 production. DTPa immunization induced a Th2 response with production of interleukin 5 and interleukin 6. Only DTPw vaccine induced higher levels of IL-12 in non-immunized mice. Our findings indicate that the co-injection of whole-cell antigens such as B. pertussis or S. typhi, modifies the anti-tetanus response shifting it from Th2 to Th1 type. However, the original Th2 immune response is not modified when the vaccine consists only of soluble antigens.

Relationship Between Sputum Inflammatory Markers and Osmotic Airway Hyperresponsiveness During Induction of Sputum in Asthmatic Patients

Hypertonic saline aerosols are being used increasingly for bronchial provocation testing and induction of sputum. The aims of this study were to assess the response to challenge with 3% hypertonic saline administered via a ultrasonic nebulizer in patients with asthma, and to evaluate relationship between % fall of FEV1 during induction of sputum (osmotic airway hyperresponsiveness; osmotic AHR) and biochemical markers of induced sputum. We investigated changes in FEV1 in response to inhaling ultrasonically nebulized 3% saline in 25 patients with asthma and 10 control subjects. FEV1 was measured before, during, and after induction of sputum. We used fluoroimmunoassay to detect eosinophil cationic protein (ECP), immunohistochemical staining to detect EG2+ (secretory form of ECP) eosinophils, and a sandwich ELISA to detect interleukin (IL)-5. Protein concentration was determined by using bicinchoninic acid protein assay reagent. Asthmatics, compared with controls, had significantly higher osmotic AHR. Moderate to severe asthmatics had significantly higher osmotic AHR compared to mild asthmatics. Osmotic AHR was significantly correlated with the proportion of eosinophils, the levels of ECP, EG2+ eosinophils, IL-5, and proteins. These data suggest that osmotic AHR is closely related to the clinical status and biochemical markers of sputum supernatant in asthmatic patients.

Differential modulatory effect of IL-5 on MHC class II expression by macrophages and B cells

The present study examines the effect of interleukin 5 on the expression of class II major histocompatibility complex (MHC) in macrophages and B cells. treatment of splenic adherent cells, a population that contains mostly macrophages and dendritic cells, with 100 U/ml of recombinant interleukin 5 resulted in a decrease of 10 to 30% in cell surface MHC class II expression by macrophages. The treatment had no effect on class I MHC expression, or on the mRNA synthesis as evaluated by tritiated-uridine incorporation. The same treatment of B cells resulted in the delineation of two groups with regard to class II MHC expression in a previously more homogeneous population. One group had an increase in surface Ia expression and the other had a decrease in the expression of this molecule. These results suggest that interleukin 5 has a role in MHC class II regulation