OBJECTIVETo observe the changing contents of leukotriene B4 ( LTB4 ), leukotriene C4 ( LTC4 ), and leukotriene D4 (LTD4 ) of lung tissue in asthmatic rats, and explore the effect of Shuanglong Capsule (SLC) on it.

METHODSSD rats were randomly divided into the nomal group, asthmatic model group, Dexamethasone group and the high, middle and low dose SLC groups. All rats except those in the normal group were sensitized by ovalbumin and challenged with the antigen, and the contents of LTB4, LTC4 and LTD4 in lung tissue of all the groups were measured by reverse phase-high performance liquid chromatography (RP-HPLC) and compared.

RESULTSThe levels of LTB4, LTC4, and LTD4 of asthmatic rats were significantly higher than those of rats in the normal group. Dexamethasone and SLC at the dose of 8. 27 g/kg or 4. 13 g/kg could significantly inhibit the production of leukotrienes of lung tissue in asthmatic rats (P <0.05).

CONCLUSIONSLC can significantly inhibit the formation of inflammatory medium LTs of lung tissue in asthmatic rats, it may be one of the key mechanisms of SLC in anti-asthma and anti-inflammatory action.

Animals ; Anti-Asthmatic Agents ; pharmacology ; Asthma ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Leukotriene B4 ; metabolism ; Leukotriene C4 ; metabolism ; Leukotriene D4 ; metabolism ; Leukotrienes ; metabolism ; Lung ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tablets

That mast cells play a role in acute allergic inflammation by releasing various inflammatory mediators, including histamine, leukotrienes (LT), such as LTC4 and LTD4, and prostaglandins (PG), such as PGD2, is well known. Additionally, mast cells contribute to the development of allergic inflammation also through the release of multifunctional cytokines. The incidence of intraepithelial mast cells (IEMC) is found to be greater in nasal mucosa exposed to an allergen, and the cells are thought to play an important role in producing the immediate allergic reaction. Lamina propira mast cells (LPMC) are known to be the dominant source of TH2 cytokine and are responsible for development of the late phases of an allergic reaction They may upregulate the expression of adhesion molecules on the endothelial cells and induce basophil and eosinophil recruitment. Based on these consideration it can be proposed that mast cell is a initiating cell of allergic reaction in target organ and IEMC and LPMC have capacity to make major contribution to both immediate or late phase reaction of allergic rhinitis.
Basophils ; Cytokines ; Endothelial Cells ; Eosinophils ; Histamine ; Hypersensitivity ; Incidence ; Inflammation ; Leukotriene C4 ; Leukotriene D4 ; Leukotrienes ; Mast Cells* ; Nasal Mucosa ; Prostaglandin D2 ; Prostaglandins ; Rhinitis*

BACKGROUND: Theophylline has been used in the treatment of asthma for decades as a broncho- dilator, but recent studies suggested that it has anti-inflammatory and immunomodulatory properties. OBJECTIVE: The aim of this study was to determine the effect of theophylline therapy on urinary excretion of leukotriene B4 (LTB4) and C4 (LTC4), which have been known to play a role in the airway inflammation in asthmatic patients. METHODS: Fifty-one patients, aged 13 months to 6 years, who were hospitalized with asthma were randomized in to 3 groups according to treatment regimen. Twenty-one patients were administered theophylline with budesonide and salbutamol inhalation (Group 1). Fifteen patients were treated with budesonide and salbutamol inhalation (Group 2) and the other fifteen patients with salbutamol inhalation only (Group 3). Urine samples for the determination of LTB4 and LTC4 were collected on admission and on the fifth hospital day in each patient. The concentrations of urinary leukotrienes were measured by ELISA (Neogen, U.S.A.) and corrected by urinary creatinine levels. Ten controls were also studied. RESULTS: The initial urinary LTC4 levels in asthmatic children were significantly higher than in controls. Urinary LTC4 was significantly decreased after treatment compared with the initial level in group 1 (p<0.05), but not in groups 2 and 3. Urinary LTB4 did not show significant difference between patients and controls on admission and showed no significant change after treatment compared with the initial levels in all three groups. CONCLUSION: These results suggest that the suppression of LTC4 synthesis is one of the anti-inflammatory mechanisms of theophylline and support the use of theophylline as a the rapeutic agent in asthmatic patients.
Albuterol ; Asthma* ; Budesonide ; Child* ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Inhalation ; Leukotriene B4* ; Leukotriene C4 ; Leukotrienes ; Theophylline*

It has been implicated that leukotrienes play roles in the pathogenesis of gastritis and gastric ulceration associated with Helicobacter pylori (H. pylori). Rebamipide is being used as an antiulcer drug but it's mechanism of action has not been understood well. One possible mechanism of action of this drug is to inhibit the cellular release of leukotrienes by various stimuli, particularly H. pylori. In the present study, attempts were made to test this possibility and the results are as follows. When Kato III cells (gastric adenoma cells) were stimulated by H. pylori, leukotriene D4 (LTD4) was released and rebamipide inhibited this release dose-dependently. Similar experiment was performed on neutrophils because the infilteration of neutrophils is a common phenomenon in H. pylori-infected gasrtric tissues. Neutrophils released LTD4 when these cells were stimulated by H. pylori and rebamipide also inhibited this release. Furthermore, rebamipide inhibited the release of LTD from neutrophils induced by calcium ionophore A23187 and arachidonic acid. The results suggest that rebamipide has the action to inhibit the release of LTD4 from various cells and this action may contribute in part to prevent the ulcerogenesis induced by H. pylori.
Adenoma ; Arachidonic Acid ; Calcimycin ; Calcium ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Leukotriene D4* ; Leukotrienes ; Neutrophils ; Stomach Ulcer

BACKGROUND: Exercise can aggravate asthmatic symptoms in many patients with bronchial asthma. It is caused by that inhaled air bypasses nasal cavity and goes directly to the lower airways through open mouth dring exercise. Although the pathogenetic mechanisms of exercise-induced asthma(EIA) have not been clarified yet, there is evidence that chemical mediators, released from the inflammatory cells triggered by airway cooling or drying, might be responsible for induction of bronchoconstriction. However, it has been controversial which chemical mediators or cells are involved in such process. Objectiye . The aim of this study was to evaluate the role of activated mast cells in the pathogenesis of EIA and find out whether or not sulfidopeptide leukotrienes (LTC4/d4/E4) are involved in the exercise-induced bronchoconstriction. MATERIAL AND METHOD: Eleven asthmatics with documented exercise-induced bronchoconstriction and 10 control subjects were studied. Before and 6 hours after free running for 6 minutes, forced expiratory volume in 1 second (FEV,) and the concentrations of N- methylhistamine, LTE4, and creatinine in unine collected for 6 hours after exercise were determined. RESULT: Urinary concentrations of N-methylhistamine(mean+SE, ng/mg creatinine) of EIA patients before and after exercise were 159+40 and 450+75, respectively. Those of control subjects were 208+ 54 and 275+ 62, respectively. Uninary N-methylhistamine levels of EIA group increased significantly after exercise, while those of control group did not change. Urinary concentrations of LTE,(mean+SE, pg/mg creatinine) of EIA patients before and after exercise were 15.6 k2.6 and 22.2+5.8, respectively. Those of control subjects were 10.4+ 4.0, 18.2 +7.0, respectively. The concentrations of LTE4 in the urine samples collected before exerise revealed no difference between EIA and control subjects (p=0.07). There was no change after exercise in both groups. Percent fall of FEV, was 29.1+8.0% (mean+SD) in EIA group and 3.4 + 4.0% in control group, respectively. There was no correlation between reduction of FEV, and change in urinary concentrations of N-methyl-histmine after exercise. CONCLUSTION: Chemical mediators of activated mast cells may be involved in exercise-induced bronchoconstriction, but there is little evidence for enhanced sulfidopeptide leukotriene generation as assessed by urinary LTE4.
Asthma ; Asthma, Exercise-Induced* ; Bronchoconstriction ; Creatinine ; Forced Expiratory Volume ; Humans ; Leukotriene E4 ; Leukotrienes ; Mast Cells ; Mouth ; Nasal Cavity ; Running

PURPOSE: Atopic dermatitis (AD) is a genetically determined, chronic relapsing skin disease. The pathogenesis of AD is complex and the course is unpredictable. Atopy is an important risk factor for the development of AD. Cysteinyl leukotrienes (Cys-LTs) were implicated in the pathophysiology of allergic diseases, and are being targeted for their diagnosis and treatments. Early detection of tissue inflammation of target organ is important to enable early prevention and management of allergic diseases. The aim of our study is to evaluate the differences in urinary leukotrienes E4 (LTE4) levels, according to AD symptom score and aeroallergen sensitization in children with AD by using noninvasive techniques. METHODS: We recruited 46 children with AD, using predetermined criteria. Clinical features of AD were evaluated by a physician, using scoring atopic dermatitis (SCORAD) index. Aeroallergen sensitization was measured by using a skin prick test and UniCap. Urine samples were also collected on day of the 1st and 2nd visits, and were analyzed for LTE4 with an enzyme-linked immunoassay kit. RESULTS: SCORAD indeces of children with AD were correlated with urinary LTE4 levels. Total immunoglobulin E (IgE) and eosinophil counts also had significant correlation with urinary LTE4 levels. Especially, aeroallergen sensitization of atopic AD significantly correlated with urinary LTE4 of these patients. CONCLUSION: Urinary LTE4 levels significantly correlated with serum total IgE and number of sensitized aeroallergen in children with AD. Clinical features of AD evaluated with SCORAD index related with urinary LTE4 level. Urinary LTE4 might be a valuable, noninvasive marker for different pathogenesis of AD.
Child ; Dermatitis, Atopic ; Eosinophils ; Humans ; Immunoassay ; Immunoglobulin E ; Immunoglobulins ; Inflammation ; Leukotriene E4 ; Leukotrienes ; Risk Factors ; Skin ; Skin Diseases

PURPOSE: Some studies report a role of leukotrienes in the pathogenesis of atopic dermatitis and suggest a rationale for the use of leukotriene receptor antagonist (LTRA) in the treatment of atopic dermatitis. This study aimed to evaluate the treatment effectiveness of montelukast in children with atopic dermatitis. METHODS: Fifty-four children between the ages of 2 and 6 years with moderate to severe atopic dermatitis were enrolled. Group A received montelukast for 8 weeks, followed by a crossover to 8 weeks of placebo after a 2-week washout period. Group B reversed the administration according to a randomized, double-blind, placebo-controlled, crossover design. The SCORing atopic dermatitis (SCORAD) index, urinary leukotriene E4 (LTE4), and eosinophil-derived neurotoxin (EDN) were assessed at every visit. RESULTS: Forty-three patients (21 males) completed the study. Although the SCORAD index was decreased in both groups, there was no statistically significant difference between montelukast and placebo (-3.0±11.2 vs -5.7±11.3, P=0.43). The level of urinary LTE4 was decreased after taking montelukast when compared to placebo, but there was no statistically significant difference (-65.9±556.2 vs 87.7±618.3, P=0.26). The changes in urinary EDN after taking montelukast and placebo had no significant difference (37.0±1,008.6 vs -195.8±916.7, P=0.10). When analyzing SCORAD indices, urinary LTE4, and EDN, we could not prove the effectiveness of montelukast in the atopic, non-atopic or high ECP (ECP ≥15 µg/L) subgroups. CONCLUSIONS: There was no statistically significant difference in clinical improvement or biomarkers between montelukast and placebo treatment. Therefore, conventional treatments with skin care and infection control might be more important strategies in the treatment of atopic dermatitis.
Biological Markers ; Child* ; Cross-Over Studies* ; Dermatitis, Atopic* ; Eosinophil-Derived Neurotoxin ; Humans ; Infection Control ; Leukotriene E4 ; Leukotrienes ; Receptors, Leukotriene ; Skin Care ; Treatment Outcome

BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin production are highly increased during inflammatory airway disorders such as, asthma, chronic bronchitis and sinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators are related with secretion and production of mucin. However, among of inflammatory mediators, the relation of leukotrienes and mucin genes expression is not clear. The aim of this study is to evaluate MUC2/5AC genes expression and mucin secretion through leukotriene receptor in human airway epithelial cells. SUBJECTS AND METHOD: The effect of Leukotriene D4 and leukotriene receptor antagonist, pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and mucin secretion was observed in the human airway NCI-H292 epithelial cells. The mRNA levels of MUC2/5AC and the amount of mucin protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoassay. RESULTS: Leukotriene D4 upregulated MUC2/5AC gene expression and mucin secretion on a dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 micrometer) downregulated the leukotriene D4-mediated MUC2/5AC gene expression and mucin secretion. CONCLUSION: These results suggest that the leukotriene receptor system is one of the expression mechanisms of MUC2/5AC genes and mucin secretion.
Asthma ; Bronchitis, Chronic ; Cytokines ; Epithelial Cells* ; Gene Expression ; Humans* ; Immunoassay ; Leukotriene Antagonists ; Leukotriene D4 ; Leukotrienes ; Lipopolysaccharides ; Mucins* ; Receptors, Leukotriene* ; RNA, Messenger ; Sinusitis

Leukotrienes (LTs) are known to act as a mediator provoking tissue response in inflammation. LTs, particularly type B4 (LTB4) as chemotactic factor of neutrophil are released from neutrophils and gastric mucosal cells when these cells are stimulated by Helicobacter pylori. The present study was performed to test a possibility that eupatilin may prevent the H. pylori-induced gastric cell damage by observing whether this chemical inhibit the release of LTB4 from H. pylori-stimulated gastric cells (Kato III) and neutrophils. As observed in the previous study, H. pylori induced the release of LTB4 from these cells and at the same influx of Ca2+ into the cells. In the presence of eupatilin, the release of LTB4 was inhibited whereas Ca2+ influx was not affected. Probably eupatilin may inhibit the release of LTB4 by preventing the synthesis of LTs. These results suggest that eupatilin can has a therapeutic effect on H. pylori-induced gasric cell damage.
Helicobacter pylori* ; Helicobacter* ; Inflammation ; Leukotriene B4* ; Leukotrienes ; Neutrophils*

BACKGROUND: Cysteinyl leukotrienes are important inflammatory mediators in bronchial asthma because they enhance microvascular permeability, increase nonspecific bronchial hyperresponsiveness, and are potent bronchoconstrictor agents. Leukotriene E4 is a major metabolite of cysteinyl leukotriene excreted in urine and its concentration of urine can be a reliable marker of the overall leukotriene production in the body. OBJECTIVE: To determine whether clinical parameters of bronchial asthma are associated with production of cysteinyl leukotrienes, expressed by urinary leukotriene E4. METHOD: We measured the urinary concentration of leukotriene E4 in bronchial asthma(127 patients) and normal control(15 persons) group by ELISA method. Pulmonary function test, allergic skin test, measurement of peripheral eosinophil count and eosinophil cationic protein were undertaken in bronchial asthma patients. RESULTS: The concentrations of urinary leukotriene E4 were significantly higher in bronchial asthma patients than normal controls (p<0.05). The increased concentrations of leukotriene E4 had a significant correlation with FEV1/FVC or methacholine PC20(p<0.05). However, the concentration of leukotriene E4 did not have any correlation with the presence of atopy, peripheral blood eosinophil count, and eosinophil cationic protein level. CONCLUSION: The concentration of urinary leukotriene E4 that represents the overall leukotriene production in the body is correlated with the degree of airway obstruction and airway hyperresponsiveness. So, the concentration of urinary leukotriene E4 may be used as an adjunctive parameter of airway obstruction and hyperresponsiveness in bronchial asthma.
Airway Obstruction ; Asthma* ; Bronchoconstrictor Agents ; Capillary Permeability ; Enzyme-Linked Immunosorbent Assay ; Eosinophil Cationic Protein ; Eosinophils ; Humans ; Leukotriene E4* ; Leukotrienes ; Methacholine Chloride ; Respiratory Function Tests ; Skin Tests