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.

Immune enhancement activities of silk lutein extract from Bombyx mori cocoons

BACKGROUND: Declining immune function poses an important clinical challenge worldwide and supplementation with natural products that possessing immune enhancing properties is a promising approach for preventing or delaying immune function decline. Cocoons from yellow silkworms are a significant source of lutein, and this unexplored silk extract could be a viable alternative source for dietary lutein. This study assessed immunomodulatory activities of the silk lutein extract. Female BALB/c mice orally received lutein, either as silk or marigold extracts (10 or 20 mg/kg daily), or vehicle only (1% tween 80 in PBS pH 7.4) for 4 weeks. Natural killer (NK) cell activity, specific antibody production, lymphocyte subpopulations, mitogen-induced lymphocyte proliferation, and cytokine production were examined. RESULTS: Silk lutein extract increased NK cell activity, and the effect was dose-related whereas marigold lutein extract was ineffective. Silk lutein extract dose-dependently enhanced antibody production in pre-immunized mice but marigold lutein extract had no effect. Feeding with silk lutein extract increased the populations of CD3+ and CD4 + CD3 + cells. Silk lutein extract also stimulated concanavalin A- and lipopolysaccharide-induced proliferations of T and B lymphocytes, respectively. Moreover, silk lutein extract increased IL-2 and IFN-γ production while the effect of marigold lutein extract was undetectable. CONCLUSIONS: Together, silk lutein extract enhanced both innate and adaptive immune functions. This preparation may prove to be an effective supplement for strengthened immunity.

Genetic polymorphisms and asthma: findings from a case - control study in the Madeira island population

BACKGROUND: Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. RESULTS: Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10mm) to house dust (1.4-fold) and storage mite (7.8-fold). CONCLUSION: In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Immunomodulatory effects of astragalus gypsicolus hydroalcoholic extract in ovalbumin-induced allergic mice model

Several studies have demonstrated that herbal extracts possess various biological effects including anti-inflammatory and anti-cancer activities. The present study was aimed to investigate the protective effects of the Astragalus gypsicolus [AG] hydroalcoholic extract in early allergic sensitized mice induced by ovalbumin. Phytochemical assay was used to recognize the main active constituents in the AG hydroalcoholic extract. Mice were immunized with subcutaneous injection of ovalbumin and aluminum hydroxide. Efficiency of sensitization was assessed by serum IgE levels and eosinophil count. After sensitization, two doses of extract [250 mg/kg and 500 mg/kg] were injected intrapritoneally. On day 14, mice were challenged with intrapritoneal injection of ovalbumin. IL-4 and IFN gamma levels in broncoalveolar lavage fluid, which had been collected on day 15, were assessed by Enzyme-Linked Immunosorbent Assay [ELISA] kit. Our results indicate two main active constituents including flavonoids and terpenoids are present in the AG.hydroalcoholic extract. Intrapritoneal injection of the AG hydroalcoholic extract was able to decrease IL-4 and increase IFN gamma. It seems the AG hydroalcoholic extract has the potential to modulate the balance of Thl/Th2 cytokines in allergy

Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice

Historically, German chamomile (GC) oil has been used for treatment of skin disorders. BALB/c mice were sensitized twice a week with 100 microL of 1% 2,4-dinitrochlorobenzene (DNCB) and challenged twice the following week with 100 microliter of 0.2% DNCB for atopic dermatitis induction. Thereafter, 3% GC oil was applied daily (70 microliter, 6 times week) on the dorsal skin for 4 weeks. Saline or jojoba oil was used for the control mice. Blood was collected after second DNCB challenge, and at 2 and 4 weeks after initiating oil application. Serum IgE levels were significantly lowered in the GC oil application group at the end of the 4-week application period. The GC oil application for 4 weeks resulted in reduction in serum IgG1 level compared with that after 2-week application. The GC oil application group showed a significantly lower serum histamine level than the control group 2 weeks after oil application. Scratching frequency of the GC oil application group was significantly lower than either control groups. This study is to demonstrate GC oil's immunoregulatory potential for alleviating atopic dermatitis through influencing of Th2 cell activation.

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.

Interleukin-13 and Its Receptors in Idiopathic Interstitial Pneumonia: Clinical Implications for Lung Function

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.

Evaluation of B-lymphocyte marker [CD19] and interleukin-4 [IL-4] in women infected with Trichomonas vaginalis

The aim of this investigation was to evaluate the B-lymphocyte subset [CD-19] and interleukin-4 [IL-4] in women injected with Trichomonas vaginalis. Vaginal swabs, washes and blood specimens were collected from 65 women attending outpatient clinic at Al-Kadhimyia Teaching Hospital in Baghdad suffering from vaginal discharge starting from January 2005, to October 2005. Twenty healthy looking age matched women were also included for control studies. Blood was taken to heparinized tubes and serum was separated. Heparinized blood was used for evaluation of the CD marker; CD-19 using the indirect immunostaining technique. The cytokine IL-4 was evaluated in serum and vaginal washes using the ELISA technique. Trichomonas vaginalis was isolated from 25 women with a prevalence rate of 38.5%. The results of CD marker showed significant differences between the infected women and controls. There was a significant increase in IL-4 in the infected women. It was found that this parasite has the ability to stimulate the cell-mediated immunity which eventually led to production of specific immunoglobulin against Trichomonas vaginalis

The effect of allergen immunotherapy on in vitro IL-4 and IFN-gamma production by peripheral mononuclear cells in house dust-sensitive Chinese patients with bronchial asthma.

The IFN-gamma produced by Th1 cells and IL-4 produced by Th2 cells are two most important cytokines in the regulation of IgE production. House dust immunotherapy has been tried in the treatment of house dust-sensitive Chinese asthmatic patients with good results. We examined the influence of such treatment on in vitro IL-4 and IFN-gamma production by peripheral blood mononuclear cells in house dust-sensitive asthmatic patients. Allergen immunotherapy in house-dust sensitive asthmatic patients can significantly decrease IL-4 production from peripheral mononuclear cells (p<0.05). The production levels of IL-4 in patients without treatment had higher levels than those in patients with hyposensitization (p<0.01). Such therapy also have some effect on promotion of IFN-gamma production in asthmatic patients. In conclusion, immunotherapy with house dust may have the potential ability to shift the Th1/Th2 balance of immune response to allergens and to create a favorable cytokine microenvironment to suppress the allergic reaction in the asthmatic airway.

Soluble interleukin-2 receptor, interleukin-4 and interferon-Gamma in bronchoalveolar lavage fluid of asthmatic patients

To clarify the role of immunoregulatory cytokines in pathogenesis of bronchial asthma, soluble interleukin-[2] receptor [sIL-[2R]], interleukin-4 [IL-[4]] and interferon- gamma [lFN-gama] as products of T -cell activation were estimated in bronchoalveolar lavage [BAL] fluid of asthmatic patients. Their levels were correlated with the degree of bronchial hyperreactivity [BHR] [PD[20]], sIL-[2R] and IL-[4] levels were significantly higher in asthmatics than normal controls. In extrinsic asthma their levels were significantly higher than that in intrinsic asthma. IL-[4] levels showed significant inverse correlation with PD[20] in extrinsic asthma. sIL-[2R] level showed insignificant inverse correlation with PD[20] in both extrinsic and intrinsic asthma, IL-[4] was poorly correlated with PD[20] in intrinsic asthma. There was no significant difference in concentration of IFN-gama between asthmatics and normal controls, however, it was slightly higher in normal control. The results of this study suggest that the elevated T-cell markers [sIL-[2R], IL-[4]] in BAL fluid from asthmatic patients is an indication that T-cell activation is present in asthma. The higher level of these cytokines in atopic asthma and their correlation with BHR suggest the preferential activation of the. TH[2]. The lower level of IFN-gama may suggest its role in the treatment of bronchial asthma and this may open the way for further studies