化浊止哮方对支气管哮喘患者肺功能及血清INF⁃γ、IL⁃4、ACTH、CORT的影响

目的:观察化浊止哮方对支气管哮喘患者肺功能、血清γ⁃干扰素(INF⁃γ)、肾上腺皮质激素(ACTH)、白介素⁃4(IL⁃4)、皮质酮(CORT)的影响。方法:将104例符合诊断标准的支气管哮喘患者随机分为对照组和观察组,每组各52例;对照组给予沙美特罗替卡松粉吸入剂(舒利迭)治疗,观察组在对照组基础上给予化浊止哮方治疗,两组疗程均为4周。比较两组患者治疗前后临床症状积分、哮喘控制测试(ACT)评分、体育活动等级量表(PARS⁃3)评分、肺功能指标、INF⁃γ、IL⁃4、ACTH、CORT水平、哮喘生活质量调查问卷(AQLQ)评分的变化;并统计两组临床疗效。结果:观察组临床症状改善效果显著优于对照组(P<0.05);与治疗前比较,治疗后两组临床症状积分、血清INF⁃γ、ACTH、CORT水平均显著降低,FEV_(1)、FEV_(1)/FVC、PEF、FEF25、FEF50、FEF75、血清IL⁃4水平及AQLQ总积分和各单项积分均显著增加(P<0.05),观察组上述指标改善均显著优于对照组(P<0.05)。结论:化浊止哮方可显著缓解支气管哮喘患者临床症状,提高肺功能、运动能力与生活质量,其机制可能与下调机体炎症反应和应激反应有关。

Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4- induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

Regulation of gene expression, growth, and cell survival by IL-4: Contribution of multiple signaling pathways

Interleukin-4 is a cytokine produced by activated T cells, mast cells, and basophils that elicits many important biological responses[1] (see Tab 1). These responses range from the regulation of helper T cell differentiation[2] and the production of IgE[3] to the regulation of the adhesive properties of endothelial cells via VCAM-1[4]. In keeping with these diverse biological effects, high-affinity binding sites for IL-4 (Kd 20 to 300 pM) have been detected on many hematopoietic and non-hematopoietic cell types at levels ranging from 50 to 5000 sites per cell[5],This review will focus on the discrete signal transduction pathways activated by the IL-4 receptor and the coordination of these individual pathways in the regulation of a final biological outcome.

EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo. IL-4 alone was found to be incapable of stimulating colony formation, but it inhibited both IL-3-and GM-CSF-induced colony formation by murine hematopoietic progenitor cells. In contrast, colony formation induced by G-CSF was enhanced in the presence of IL-4. We also studied the influence of IL-4 on hematopoietic reconstiution after allogeneic bone marrow transplantation in a murine medel, and found that IL-4 had significant inhibitory effects on neutrophil recovery and that neutrophil recovery accelerated by IL-3 and G-CSF was significantly suppressed by IL-4. The combination of IL-4 and GM-SF caused a significant decrease in the absolute number of neutrophils.

Association between interleukin-4 polymorphisms and asthma

Objective:To perform a systematic review and meta analysis on the association of C-589T and C-590T polymorphisms of IL-4 with asthma and to estimate allele frequencies, the magnitude of the gene effect as well as the possible mode of inheritance. Methods: A genetic model-free approach was used to perform a meta analysis. Heterogeneity, sensitivity analysis and publication bias were also explored. Results: Our meta analysis summarized the evidence to date regarding the association of C-589T and C-590T polymorphisms in the promoter region of IL-4 gene with asthma. For C-590T, the results showed a significant recessive genetic model, and the CC genotype was about 24% less likely to have asthma than the genotype CT and TT. Although there was evidence suggesting a recessive genetic model for C-589T, the recessive model was not statistically significant. Conclusion: This meta analysis suggests that there may be an important effect of single nucleotide polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of asthma.

Therapeutic effects of four strains of probiotics on experimental colitis in mice

AIM:To investigate the therapeutic effects of four strains of probiotics(E.feacalis,L.acidophilus,C.butyricum and B.adolescentis) on dextran sulphate sodium(DSS)-induced experimental colitis in Balb/c mice.METHODS:Eighty Balb/c mice were randomly divided into 8 groups.Weight-loss,fecal character,fecal occult blood and hematochezia were recorded daily.Disease activity index(DAI) scores were also evaluated everyday.Length of colon was measured and histological scores were evaluated on the 13th day.Myeloperoxidase(MPO) activity was detected.Interleukin-1(IL-1) and IL-4 expression was detected by ELISA and RT-PCR.RESULTS:The four strains of probiotics relieved the inflammatory condition of DSS-induced experimental colitis in mice.Weight loss was slowed down in all probiotics-treated mice.Even weight gain was observed by the end of probiotics treatment.The DAI and histological scores of probiotics-treated mice were lower than those of mice in the control group(1.9 ± 0.2 vs 8.6 ± 0.4,P < 0.05 for E.faecalis).The length of colon of probiotics-treated mice was longer than that of mice in the control group(10.3 ± 0.34 vs 8.65 ± 0.77,P < 0.05 for E.faecalis).The four strains of probiotics decreased the MP activity and the IL-1 expression,but increased the IL-4 expression.E.faecalis had a better effect on DSS-induced experimental colitis in mice than the other three strains.CONCLUSION:The four strains of probiotics have beneficial effects on experimental colitis in mice.E.faecalis has a better effect on DSS-induced experimental colitis in mice than the other three strains.Supplement of probiotics provides a new therapy for UC.

T-Helper I Cell/T-Helper 2 Cell Balance with Anti Inflammatory Therapy in Partly Controlled Asthmatic Children

The authors aimed to assess Thl （T-helper cell 1）/Th2 （T-helper cell 2） balance, through evaluation of serum IFN-γ （interferon gamma） and IL-4 （interleukin 4）, during asthma exacerbation and study the effect of anti inflammatory therapy. A randomized prospective case-control study was designed. The sludy included 30 asthmatic patients, aging 8-14 years. All were diagnosed as partly controlled asthmatics. Twenty, age and sex matched, healthy children were included in the study as control group All participants were subjected to medical history, clinical examination, pulmonary function testing, eosinophilic blood counting, estimation of serum interleukine-4 and interferon gamma. Patients were treated for 6 weeks with 2 different anti inflammatory drugs. All methods were then repeated for follow up. IL-4 serum level was significantly higher in subjects with partly controlled asthma than in control subjects （P = 0.01）, and then in asthmatic patients after therapy （P = 0.0000）, while IFN-）, serum level was significantly lower in subjects with partly controlled asthma than in control subjects （P = 0.01）, and than in asthmatic patients after therapy （P = 0.0000）. Interferon gamma showed a significant negative correlation with IL-4 among the healthy control group （r = -0.559, P = 0.010）. Both LTA （leukotriene antagonist） and ICS （inhaled corticosteroids） therapy lead to significant improvement, but there were no statistically significant differences （P 〉 0.05） between them as regard the pulmonary functions and the laboratory evaluating parameters. Both serum levels of IL-4 and IFN-γ, could be used as a reliable inflammatory biomarker for the evaluation and follow up of asthmatic patients.

Cloning and polymorphism analysis of IL-4 proximal promoter in asthmatic children

OBJECTIVE: To clone and study the polymorphism within interleukin-4 (IL-4) proximal promoter of asthmatic children. METHODS: The IL-4 proximal promoter segments were amplified and selected by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) with genomic DNA from ten healthy children and forty patients with dominantly allergic familial histories as templates. The selected PCR segments were cloned into recombinant plasmids pIL-4-Jx2. The PCR inserts were sequenced by dideoxy chain termination method. RESULTS: Seven aberrant bands were found in SSCP analysis from forty asthmatic patients. The sequencing results showed that four variant sites were found within or adjacent to the known IL-4 regulatory element. A C to A transversion located at -229 position was just within the positive regulatory element-I (PRE-I) in one patient. A C to T transition adjacent to the negative regulatory element-II (NRE-II) and an extra G adjacent to TATA box were found in two patients. A five base nucleotide deletion was found near signal transducers and activators of transcription-6 responsive element (STAT-6 RE) in one patient. CONCLUSION: There were polymorphisms within the IL-4 proximal promoter of allergic asthmatic patients and these polymorphisms might result in aberrant expression of IL-4 gene and asthma.

Effects of Electroacupuncture at Shangjuxu (ST 37) on Interleukin-1β and Interleukin-4 in the Ulcerative Colitis Model Rats

Objective： To probe into the mechanisms of electroacupuncture （EA） at Shangjuxu （ST 37） for treatment of the ulcerative colitis （UC）. Methods： Forty male Wistar rats were randomly divided into 4 groups： a normal group, a model group, a Shangjuxu group and a non-acupoint group, 10 rats in each group. The UC rat model was made with enema of trinitro-benzenesulfonic acid （TNBSA）, and the changes of interleuldn-1β （IL-1β） and interleukin-4 （IL-4） contents after EA at Shangjuxu （ST 37） were observed. Results： EA at Shangjuxu （ST 37） could significantly decrease the IL-1β content and increase the IL-4 content in the colic tissues of the UC rats with significant differences as compared with the model group and the non-acupoint group （P〈0.05 or P〈0.01）. Conclusion： The mechanisms of EA at Shangjuxu （ST 37） for treatment of the UC rats is possibly related with the decrease of IL-1β, a inflammation-promoting cytokine, and the increase of IL-4, a anti-inflammatory cytokine.

Experimental studies on the treatment and pathological basis of combined radiation and burn injury

OBJECTIVE: To investigate therapeutics for and the pathological basis of combined radiation and burn injuries. METHODS: Combined radiation and burn injuries on mice and rats were inflicted by gamma ray irradiation from a (60)Co source and thermal radiation from a 5 kW bromotungsten lamp. RESULTS: The dysfunction of myocardium played an important role in the development of early stage shock. Transfusion of irradiated (in vitro, 20 Gy) or stored (4 degrees C, 7 days) blood after irradiation was done to promote the success of allo-transplantation of bone marrow. Decrease of IL-4 mRNA expression was the molecular basis of depression of intestinal mucosa immune and intervention of IL-4 showed an antagonistic effect on enterogenic infection. A new lipid component extracted from burn eschar was documented for the first time and its toxic effects were elucidated. The survival rate of alloskin grafts after removal of burn eschar from the recipient animals was obviously increased in combined injury due to reduction of immune rejection activity by the radiation effect. In contrast, in animal models with simple burn, the alloskin grafts were all rejected within ten days after the procedure. A successful therapeutic result (survival rate: 92% for 30 days and 67% for 100 days) was obtained by comprehensive management of treated animals, while the untreated control animals all died within 3 - 7 days after injury. CONCLUSION: The pathogenesis of injury caused by simultaneous radiation and burn is extremely complicated and the treatment is very difficult. A comprehensive management program consisting of several therapeutic measures aimed at key links of the pathogenesis may achieve significantly improved results.

T helper cells in patients with chronic hepatitis B virus infection

OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transform growth factor-beta (TGF-beta) in single CD4(+) T cells isolated from peripheral blood mononuclear cells (PBMCs) and the role of polarized Th cell populations in chronic HBV-infection was discussed. METHODS: PBMCs from chronically infected HBV individuals were isolated, stimulated by PMA/Ionomycin/Monensin, and IL-4, IFN-gamma and TGF-beta production by CD4(+) T cells was determined by using fluorescence activated cell sorter (FACS) analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta-producing T cells ranged from 2.3% - 18.6%, 1.1% - 8.7% and 0.7% - 7.1% respectively in CD4(+) T cells from non-infected individuals. Most of CD4(+) T cells from PBMCs in chronically infected HBV individuals were Th0 cells. The proportion of Th1 cells increased significantly with hepatic inflammatory activity, and in the active period of chronic hepatitis B infection were higher than those in the non-active period (P 0.05), but were higher than that from controls (P

Nuclear factor-κB in signal conduction of protein kinase C in T lymphocytes from an asthmatic guinea pig model

Objective To explore the role of nuclear factor κB (NF κB) in the signal conduction of protein kinase C (PKC) regulated proliferation, apoptosis and expression of Th2 cytokines - interleukin 4 (IL 4) and interleukin 5 (IL 5) of T lymphocytes in the bronchial alveolus lavage fluid (BALF) Methods T lymphocytes were isolated and purified from BALF of asthmatic guinea pigs in normal and asthmatic groups, and were stimulated with PKC agitator phorbol 12 myristate 13 acetate (PMA) and NF κB inhibitor pyrrolidine dithiocarbamate (PDTC), respectively The expressions of NF κB, IL 4 and IL 5 mRNA and protein, the proliferation and apoptosis of T lymphocytes were observed by immunohistochemistry, in situ hybridization, ELISA, MTT and TUNEL, respectively Results The activation of NF κB, proliferation response, and expression of IL 4 and IL 5 mRNA and protein in T lymphocytes stimulated by PMA were significantly higher than those of their blank control ( P 【0 01), while those indexes of T lymphocytes stimulated by PMA and PDTC simultaneously were significantly lower than those stimulated by PMA alone ( P 【0 01) The apoptotic index of T lymphocytes stimulated with PMA were significantly lower than that of their blank control ( P 【0 01), and the apoptotic index of asthmatic guinea pig T lymphocytes stimulated with PMA and PDTC simultaneously were significantly higher than that stimulated by PMA alone ( P 【0 01) The significant positive correlations were found between the activation of NF κB and the proliferation ( r =0 64, P 【0 001), and the expression of IL 4 and IL 5 mRNA and protein of T lymphocytes, respectively ( r =0 55-0 68, P 【0 001) There was also significant negative correlation between the activation of NF κB and apoptosis of T lymphocytes ( r =0 62, P 【0 001) Conclusions NF κB may participate in the signal conduction of PKC regulated proliferation, apoptosis and expression of IL 4 and IL 5 of T lymphocytes in asthma The activation of NF κB in PKC signal conduction pathway of T lymphocytes may play an important role in the pathogenesis of asthma

Clinical efficacy of acupuncture in treatment ofchronic urticaria and its effects on the content of IgE and the imbalance of Th1/Th2 cell function

Objective:To observe the clinical efficacy of acupuncture in treatment of chronic urticaria and the change in the content of serum immunoglobulin E(IgE),and to discuss the effect of acupuncture on the imbalance of T helper(Th)1/Th2 cell function via observing the changes in the contents of interferon-y(IFN-y)and interleukin-4(IL-4).Methods:Ninety patients meeting the inclusion criteria of chronic urticaria were randomized into an acupuncture-medication group,an acupuncture group and a Western medication group by the random number table method.The acupuncture-medication group was intervened by acupuncture,cupping,collateral-pricking bloodletting and oral administration of cetirizine hydrochloride tablets;the acupuncture group was treated with acupuncture,cupping and collateral-pricking bloodletting;the Western medication group only received oral administration of cetirizine hydrochloride tablets.Before treatment and after 6-week treatment,the changes in the symptom scores and the contents of serum IgE,IFN-γ and IL-4 in the three groups were observed.Results:There were no significant differences in the total effective rate among the three groups(all P>0.05),but the cured and markedly effective rate was significantly higher in the acupuncture-medication group than that in the Western medication group(P<0.05).After treatment,the total symptom score decreased in the three groups(P<0.05),and the improvement of total symptom score in the acupuncture-medication group was more significant than that in the Western medication group(P<0.05).The component symptom scores all decreased after treatment in the three groups(all P<0.05);the improvements of the scores of itch intensity,and skin lesion size and number were more significant in the acupuncture-medication group than in the Western medication group(all P<0.05);the improvement of the skin lesion size score was more significant in the acupuncture group than in the Western medication group(P<0.01).The contents of IgE and IL-4 dropped(all P<0.05)and the content of IFN-y increased(P<0.05)after treatment in the three groups;the post-treatment changes in the serum contents of IgE and IFN-y were more significant in the acupuncture-medication group than in the Western medication group(both P<0.05).The incidence rate of adverse reactions was significantly lower in the acupuncture-medication group and acupuncture group than in the Western medication group(both P<0.05),and the relapse rate was significantly lower in the acupuncture-medication group than in the Western medication group(P<0.05).Conclusion:Combined acupuncture and medication can enhance the cured and markedly effective rate in treating chronic urticaria.Acupuncture is equivalent to cetirizine hydrochloride tablets comparing the clinical efficacy in treatment of chronic urticaria.Acupuncture plus medication and acupuncture alone both can effectively mitigate the clinical symptoms,with low incidence of adverse reactions.The relapse rate is low when using acupuncture together with medication.Acupuncture plus medication can work better in regulating the contents of IgE and IFN-y and improving the imbalance of Th1/Th2 cell function.

Immunogenicity analysis following human immunodeficiency virus recombinant DNA and recombinant vaccinia virus Tian Tan prime-boost immunization

This study assessed and compared the immunogenicity of various immunization strategies in mice using combinations of re- combinant DNA （pCCMp24） and recombinant attenuated vaccinia virus Tian Tan （rddVTT_ccMpe4）. Intramuscular immuniza- tion was performed on days 0 （prime） and 21 （boost）. The immunogenicity of the vaccine schedules was determined by meas- uring human immunodeficiency virus （HIV）-specific binding antibody levels and cytokine （interleukin-2 and interleukin-4） concentrations in peripheral blood, analyzing lymphocyte proliferation capacity against HIV epitopes and CD4~/CD8＋cell ratio, and monitoring interferon-gamma levels at different times post-immunization. The results showed that pCCMp24, rddVTT.ccMp24 and their prime-boost immunization induced humoral and cellular immune responses. The pCCMp24/ rddVTT.ccMp24 immunization strategy increased CD8＋ T cells and induced more IFN-7-secreting cells compared with sin- gle-shot rDNA. The prime-boost immunization strategy also induced the generation of cellular immunological memory to HIV epitope peptides. These results demonstrated that prime-boost immunization with rDNA and rddVTT_ccMp24 had a tendency to induce greater cellular immune response than single-shot vaccinations, especially IFN-7 response, providing a basis for further studies.