OBJECTIVE: To observe the effects of acupuncture combined with bloodletting on the expression of inflammatory factors in serum, the morphology of sensitized skin tissue and the mast cell degranulation in urticaria rats, and to explore the potential mechanism of this therapy for urticaria. METHODS: Among 42 SD rats of SPF grade, 6 rats were randomly collected for the preparation of sensitized antiserum; and the rest 36 rats were randomized into a blank group, a model group, a positive drug group, an acupuncture group, a bloodletting group and a combined treatment group (acupuncture + bloodletting), 6 rats in each one. The rat model of urticaria was established by passive cutaneous anaphylaxis. In the positive drug group, loratadine (1 mg•kg^-1) by gavage was administered once a day. In the acupuncture group, 1 h after gavage with 0.9% NaCl (1 mL), acupuncture was delivered at "Baihui" (GV 20), "Zhongwan" (CV 12), and bilateral "Quchi" (LI 11) and "Xuehai" (SP 10) for 15 min, once daily . In the bloodletting group, 1 h after gavage with 0.9% NaCl (1 mL), bloodletting was operated at "Dazhui" (GV 14) and bilateral "Geshu" (BL 17), around 0.1 mL of bleeding volume at each point, once daily. In the combined treatment group, 1 h after gavage with 0.9% NaCl (1 mL), the interventions as the acupuncture group and the bloodletting group were adopted, once daily. All the interventions started on day 6 of modeling, lasting 2 weeks. After intervention completion, antigenic stimulation was performed in the rats of each group. Using ELISA, the levels of serum immunoglobulin E (IgE), tryptase (TPS), interleukin-4 (IL-4), interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α) were detected. The diameter of the blue spots of the sensitized skin on the back was measured with ruler in each rat. The morphology of sensitized skin tissue was observed using HE staining, and the degranulation of mast cells was observed using Toluidine blue staining. RESULTS: Compared with the blank group, in the model group, the levels of serum IgE, TPS, IL-4, IL-5 and TNF-α increased (P<0.01), the diameter of blue spot on the sensitized part of the rat back was larger (P<0.01), the degranulation rate of mast cells was elevated (P<0.01), and there were obvious inflammatory cell infiltration and edema in the dermis of sensitized skin tissue on the rat back. Compared with the model group, the serum levels of IgE, TPS, IL-4, IL-5 and TNF-α were reduced in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group (P<0.01, P<0.05); skin blue spot diameter was smaller in the positive drug group and the combined treatment group (P<0.05); the degranulation rate of mast cells decreased in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group (P<0.01); and the dermal edema, inflammatory infiltration were attenuated in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group. Compared with the acupuncture group and the bloodletting group, the serum levels of IgE, TPS, IL-4, IL-5 and TNF-α, as well as the degranulation rate of mast cells in the sensitized tissue were lower in the positive drug group and the combined treatment group (P<0.05). CONCLUSION Acupuncture combined with bloodletting effectively suppress mast cell degranulation in the sensitized skin tissue on the back of urticaria rats, and ameliorate the histopathological morphology. Its effect mechanism may be related to inhibiting the differentiation and proliferation of helper T cells 2 and regulating the humoral immune response.
Animals ; Rats ; Mast Cells/immunology* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Male ; Cell Degranulation ; Humans ; Bloodletting ; Urticaria/immunology* ; Female ; Acupuncture Points ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-4/blood* ; Interleukin-5/blood* ; Combined Modality Therapy ; Immunoglobulin E/blood* ; Disease Models, Animal

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Cytokines/metabolism* ; Interleukin-10 ; Interleukin-17/metabolism* ; Interleukin-6/metabolism* ; Interleukin-5/metabolism* ; Blood Coagulation Disorders ; Ferritins ; Tretinoin

BACKGROUND/AIMS: Role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation. METHODS: We recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays. RESULTS: No associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p < 0.05); CC/TT genotype at ATG5 8830C>T associated with lower FEV1% predicted value (p < 0.05). DNA fragments containing ATG5 -769T and -335G alleles had higher promoter activities compared to those with -769C and -335A in both human airway epithelial cells (A549, p < 0.01) and human mast cell (HMC-1, p < 0.001). GG and CC genotype at ATG7 -100A>G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants). CONCLUSIONS: Genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.
Adolescent ; Adult ; Asthma/blood/*genetics/immunology/pathology ; Autophagy/*genetics ; Autophagy-Related Protein 5/*genetics ; Autophagy-Related Protein 7/*genetics ; Case-Control Studies ; Cell Line ; Female ; Gene Frequency ; Genes, Reporter ; Genetic Predisposition to Disease ; Haplotypes ; Heterozygote ; Homozygote ; Humans ; Interleukin-8/blood ; Male ; Middle Aged ; Neutrophil Infiltration/*genetics ; Neutrophils/immunology/metabolism/*pathology ; Phenotype ; *Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors ; Severity of Illness Index ; Transfection ; Young Adult

OBJECTIVE: To observe changes of serum Th1/Th2 cytokines and IgE of rats with experimental allergic rhinitis (AR) treating with Scoparone (20 ml/kg, the concentration is 168 mg/L). METHOD: Forty male SD rats were randomly divided into 4 groups : group NC, group AR, group Sco, group Dxm. The rats were sensitized with OVA and were then treated with Scoparone, during the treatment, the behaviors were observed and the change in nasal mucosa were recorded. The level of serum cytokines IFN-gamma, IL-4, IL-5 and IgE were determined by ELISA. RESULTS: The behavior scores of group Sco were significantly lower than those of group AR, the difference was statistically significant (P < 0.01). Comparing to group Dxm and group NC respectively, the difference was not statistically significant (P > 0.05). The nasal inflammation of group Sco was significantly less than that of group AR. The level of serum IFN-gamma of group Sco was significantly higher than that of group AR, while the levels of serum IgE, IL4, IL-5 of group Sco were significantly lower (P < 0.01). There were no significantly difference between group Sco and group NC, group Dxm, the difference was not statistically significant (P > 0.05). CONCLUSION Scoparone is highly effective in treating allergic rhinitis by regulating the expression of Th1/Th2 cytokines and IgE.
Animals ; Coumarins ; pharmacology ; Disease Models, Animal ; Immunoglobulin E ; blood ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Interleukin-5 ; blood ; Male ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; drug therapy ; Th1-Th2 Balance ; drug effects

PURPOSE: The nephrotic syndrome (NS) is characterized by the favorable response to glucocorticoid therapy and the development of NS may be associated with dysfunctional immune systems. In order to investigate the serum immunoglobulin E (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid responsive NS patients and 5 healthy controls were enrolled in this study. MATERIALS AND METHODS: All patients were divided into two groups according to the initial serum IgE levels, such as normal and high IgE group, and their clinical characteristics were evaluated. In addition, serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-beta were compared and correlated with serum albumin, proteinuria by means of disease severity, and cytokines. RESULTS: In the high IgE group, the higher comorbidity of allergic diseases and relapsing rate, the longer duration of steroid therapy before initial remission, and the higher serum IL-4 and IL-5 levels were found. In all patients, initially higher serum levels of IL-4 and IL-5 declined to normal levels after steroid therapy, whereas the serum IL-10 levels showed no significant difference between nephrotic phase (heavy proteinuria) and remission phase (no proteinuria) of NS. The serum TGF-beta levels of the nephrotic phase were significantly lower than those of remission phase or control group, and returned to normal control levels after steroid therapy. CONCLUSION: This study indicates that initial IgE level is associated with steroid responsiveness and disease severity, and cytokine activities may also be related to the pathogenesis of pediatric steroid responsive NS.
Adolescent ; Child ; Child, Preschool ; Cytokines/*blood ; Female ; Humans ; Immunoglobulin A/blood ; Immunoglobulin E/*blood ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Infant ; Interleukin-4/blood ; Interleukin-5/blood ; Male ; Nephrotic Syndrome/*blood/*drug therapy ; Steroids/*therapeutic use ; Transforming Growth Factor beta/blood

OBJECTIVE: To analyze Th1 and Th2 immune balance related cytokines and clinical significance in obstructive sleep apnea hypopnea syndrome children without allergic rhinitis and asthma. METHOD: Collected 91 cases of obstructive sleep apnea hypopnea syndrome children with obstructive level data, and measured the serum Th1 cytokine TNF-beta and IFN-gamma, Th2 cytokines IL-4 and IL-5 levels. One hundred and five normal children were enrolled for the same detection of serum cytokines. RESULT: Non-allergic rhinitis and asthma children serum levels of IFN-gamma was lower than control group children, the difference was statistically significant (P < 0. 01). Other cytokines (TNF-beta, IL-4 and IL-5) were no significant difference with the control group. CONCLUSION Th1 and Th2 immune response was imbalance in non-allergic rhinitis and asthma obstructive sleep apnea hypopnea syndrome children. The decline in Th1 cell-mediated protective immune response cells may cause disease.
Asthma ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Interleukin-5 ; blood ; Lymphotoxin-alpha ; blood ; Male ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; Sleep Apnea, Obstructive ; blood ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

OBJECTIVETo observe the effect of Ziyinqingsang decoction on the levels of interleukin-4 (IL-4) and IL-5 in the peripheral blood mononuclear cells (PBMCs) in children with cough variant asthma (CVA) in the acute stage.

METHODSThirty children with CVA in the acute stage were given Ziyinqingsang decoction for 2 weeks. The IL-4 and IL-5 levels in the PBMCs were determined using ELISA before and after the treatment, and the changes of the clinical symptoms were observed.

RESULTSThe levels of IL-4 and IL-5 in the PBMCs was 89.69∓13.82 ng/l and 12.17∓0.43 ng/ml before the treatment, which were significantly reduced to 72.18∓14.89 ng/l and 5.81∓0.31 ng/ml after the treatment (P<0.05). The symptoms including coughing, pharyngodynia, and pharyngo-itch were all improved obviously (P<0.05).

CONCLUSIONZiyinqingsang decoction ameliorates the symptoms of CVA in the acute stage probably by decreasing the levels of IL-4 and IL-5 in the PBMCs of the children.

Asthma ; blood ; drug therapy ; Child ; Cough ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interleukin-4 ; blood ; Interleukin-5 ; blood ; Leukocytes, Mononuclear ; Male ; Phytotherapy

OBJECTIVETo investigate the effects of polyinosinic-polycytidylic acid (polyI:C) on the production of thymic stromal lymphopoietin (TSLP) and airway inflammation in mice with exacerbated asthma induced by respiratory syncytial virus (RSV).

METHODSThirty-two female BALB/c mice were randomly divided into 4 groups, namely the PBS control group, OVA group, OVA/RSV group, and OVA/RSV/polyI:C group. In the latter 3 groups, the mice were sensitized by OVA and stimulated with nebulized OVA. RSV was inoculated into the nasal cavity of the sensitized mice and polyI:C (1 mg/kg) was intramuscularly administered. The airway response to metacholine was examined, and the serum levels of IL-4, IL-5, IL-13, and IFN-γ and TSLP in the supernatants of bronchoalveolar lavage fluid (BALF) were detected using ELISA. The total BALF cells, eosinophils, lymphocytes and neutrophils were counted. The lung specimens were collected to observe the inflammation with HE staining, and immunohistochemistry was employed to determine TSLP production in the airway epithelial cells.

RESULTSThe mice in RSV/OVA/polyI:C group showed a significantly lower airway responsiveness to metacholine than those in OVA/RSV group (P<0.01). Compared with OVA/RSV group, RSV/OVA/polyI:C group showed significantly lower serum levels of IL-4, IL-5, IL-13 and TSLP in BALF (P<0.05), with also lower total BALF cells, eosinophils and lymphocytes (P<0.05) and lessened infiltration of the airway inflammatory cells. Immunohistochemistry of TSLP also demonstrated a lower production of TSLP in the airway epithelial cells in RSV/OVA/polyI:C group than in OVA/RSV group.

CONCLUSIONSpolyI:C can inhibit the increase in TSLP production in the airway epithelial cells after RSV infection and relieve airway inflammation in mice with RSV-induced asthma exacerbation.

Animals ; Asthma ; blood ; metabolism ; virology ; Bronchoalveolar Lavage Fluid ; Cytokines ; secretion ; Female ; Inflammation ; pathology ; Interleukin-13 ; blood ; Interleukin-4 ; blood ; Interleukin-5 ; blood ; Mice ; Mice, Inbred BALB C ; Poly I-C ; pharmacology ; Respiratory Syncytial Virus Infections ; blood ; metabolism ; Respiratory Syncytial Viruses

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.
Animals ; Antibodies, Helminth/blood ; Chemokine CCL11/biosynthesis ; Cytokines/biosynthesis ; Female ; Gene Expression Profiling ; Immunoglobulin E/blood ; Interleukin-13/secretion ; Interleukin-4/secretion ; Interleukin-5/secretion ; Interleukins/biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor, PAR-2/*metabolism ; Th2 Cells/*immunology ; Trichinella spiralis/*immunology ; Trichinellosis/*immunology

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammation of the skin that often appears in early childhood. The manifestation is related to the tendency towards T helper 2 cytokine immune responses (interleukin (IL)-4, IL-5). Genetic factors are suggested to play important roles in AD, and it can be transmitted to newborns, increasing their risk of developing allergies. OBJECTIVE: To determine the association between cord-blood cytokine levels (IL-5, interferon (IFN) γ), cord-blood total immunoglobulin E (IgE) level, perinatal environmental exposure, and the risks of allergy as well as the development of AD in the first 6 months of life. METHODS: A 6-month cohort study with a nested case-control within was conducted on newborns in Jakarta from December 2008 until May 2009. After the umbilical cord blood samples were taken and stored, subjects were followed up monthly until 6 months old. The occurrence of AD and lifestyle or environmental exposures were recorded. The allergic risk was determined using a modified pediatric allergy immunology work groups scoring system based on allergic history (allergic rhinitis, asthma, AD) in the family. The levels of IL-5 and IFN-γ were measured using ELISA and total IgE by CAP system FEIA. Multivariate analysis was used to evaluate risk factors. RESULTS: This study was conducted on 226 subjects. The incidence of AD was 16.4%; of those, 59% had low risk allergy, 38.5% moderate, and 2% high risk. AD mostly occurred at the age of 1 month (57%). Cord blood samples were examined in 37 subjects with AD and 51 without AD; of those, 25% showed high levels of total IgE (>1.2 IU/µL), and 51% showed normally-distributed high absorbance IL-5 values (≥0.0715, absolute value was undetected). The increased level of IL-5 was directly proportional to IgE. High absorbance IFN-γ values (≥0.0795, absolute value = 18.681 pg/µL) were observed in 52% of subjects. CONCLUSION: The associations between the risk of allergy in the family, cord-blood total IgE, IL-5, IFN levels, and some perinatal environmental exposure with AD in the first 6 months of life have not been established.
Allergy and Immunology ; Asthma ; Case-Control Studies ; Cohort Studies ; Dermatitis, Atopic ; Environmental Exposure ; Enzyme-Linked Immunosorbent Assay ; Fetal Blood ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Incidence ; Infant, Newborn ; Inflammation ; Interferons ; Interleukin-5 ; Life Style ; Multivariate Analysis ; Rhinitis ; Risk Factors ; Skin