Levels Of Th1-type Cytokines Research Articles

SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway.

Conventional allergic rhinitis (AR) treatments have limitations due to the lack of safety and complete cure strategy. We evaluated the effects of silent information regulator 1 (SIRT1), a multifunctional molecule involved in a variety of inflammatory pathways, on murine AR model. Ovalbumin (OVA)-induced murine model was constructed, and recombinant SIRT1 was administered into the nostril continuously. The expression of SIRT1 was measured at mRNA and protein levels, and the allergic symptoms were evaluated. Protein levels of OVA-specific IgE, leukotriene C4 (LTC4), eosinophil cation protein (ECP), prostaglandin D2 (PGD2), as well as different inflammatory cytokine mediators in the serum and nasal lavage fluid (NLF), were assessed by ELISA. The effects of SIRT1 on human primary nasal epithelial cells challenged with tumour necrosis factor (TNF)-α were also evaluated by investigating the HMGB1/TLR4 signalling pathway. Administration of SIRT1 significantly alleviated OVA-induced AR symptoms with lower numbers of sneezing and nasal rubbing events, decreased levels of OVA-specific IgE, LTC4, ECP, PGD2, less inflammatory cells and downregulated levels of Th2 type cytokines. SIRT1 also reduced the genes of HMGB1/TLR4 signalling pathway in the murine model and cultured human nasal epithelial cells. Expression of SIRT1 is impaired in OVA-induced AR model. The administration of SIRT1 alleviates the allergic symptoms of mice, regulates the production of pro-inflammatory mediators predominantly produced by Th2 cells in AR and attenuates expressions of proteins relevant to HMGB1/TLR4 signalling pathway. All the results showed that SIRT1 is promising as a therapeutic agent of AR.

Gene cloning, expression and immune adjuvant properties of the recombinant fusion peptide Tα1-BLP on avian influenza inactivate virus vaccine

Thymosin α1 (Tα1) and bursin-like peptide (BLP) are both immunopotentiators. In order to investigate adjuvant of thymosin α1-bursin-like peptide (Tα1-BLP), we cloned the gene of Tα1-BLP and provided evidence that the gene of Tα1-BLP in a recombinant prokaryotic expression plasmid was successfully expressed in E. coli BL21. To evaluate the immune adjuvant properties of Tα1-BLP, chickens were immunized with Tα1-BLP combined with H9N2 avian influenza whole-inactivated virus (WIV). The titers of HI antibody, antigen-specific antibodies, AIV-neutralizing antibodies, levels of Th1-type cytokines (IFN-γ) and Th2-type cytokines (IL-4) and lymphocyte proliferation responses were determined. What's more, the viral loads and pathologic changes of lung tissue were observed by virus challenge experiment and HE staining to evaluate the immune protection of chickens. We found that Tα1-BLP enhanced HI antibody and antigen-specific IgG antibodies titers, increased the level of AIV-neutralizing antibodies, induced the secretion of Th1- and Th2-type cytokines, and promoted the proliferation of T and B lymphocyte, Furthermore, virus challenge experiment and HE staining confirmed that Tα1-BLP contributed to inhibition replication of the virus from chicken lungs and protected the lungs from damage. Altogether, this study suggested that Tα1-BLP is a novel adjuvant suitable for H9N2 avian influenza vaccine.

Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype

CD4+ T cells that co-express CD25 and CD127 (CD25+CD127+) make up around 20% of all circulating CD4+ memory T cells in healthy people. The clinical significance of these cells is that in children with type 1 diabetes their relative frequency at diagnosis is significantly and directly correlated with rate of disease progression. The purpose of this study was to further characterize the CD25+CD127hi cells. We show that they are a mix of Th1 and Th2 cells however, they have a significantly higher relative frequency of pre-committed and committed Th2 cells, and secrete significantly higher levels of Th2-type cytokines than CD25− memory T cells. Further, these cells are neither exhausted nor senescent and proliferate to the same extent as CD25− memory cells. Thus, CD25+CD127hi cells are a highly active subset of memory T cells that might play a role in controlling inflammation via anti-inflammatory Th2-type deviation.

The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Recurrent respiratory tract infections in young children, especially viral infections, are the major cause of acute asthmatic exacerbations and contribute to development of asthma. Bacterial extracts have been used to improve the immune defenses of the respiratory tract. However, seldom studies have examined the effect of bacterial lysates on childhood asthma. In this study, we examined whether bacterial lysates (OM-85) will improve symptoms of asthmatic mice via modulation of the immune response. Asthmatic mice models were established with OVA challenge and treated with oral administration of Broncho-Vaxom (OM-85). Next, infiltrations of inflammatory cells including eosinophil and neutrophils were examined. Pulmonary tissues in asthmatic mice models were analyzed by hematoxylin and eosin (HE) staining. The levels of Th1/Th2-typed cytokines in bronchoalveolar lavage fluid (BALF) of asthmatic mice models were examined by enzyme-linked immunosorbent assay. Compared to control group, we found significant reduction of airway wall thickness, luminal stenosis, and mucus plug formation in asthmatic mice models after oral administration of OM-85. The infiltrations of eosinophil were also significantly decreased in BALF in asthmatic mice models. Oral administration of OM-85 was shown to suppress Th2-type cytokine levels. Our findings provide evidence that oral administration of OM-85 is capable of attenuating airway inflammation in asthmatic mice models. Oral administration of OM-85 may have a positive impact in terms of asthma severity.

Design and immunogenicity evaluation for the bacteria-like particle vaccine against swine type O foot-and-mouth disease virus

Based on gram positive enhancer matrix displaying technology, we designed and evaluated a bacteria-like particle vaccine against swine type O Foot-and-mouth disease virus. Three optimized genes of type O Foot-and-mouth disease virus strain Mya98 were cloned into recombinant prokaryotic expression vector pQZ-PA and renamed as pQZ-BT1B-PA, pQZ-BT2B-PA and pQZ-B (T1BT2) 4B-PA, fused with an anchor protein (PA) binding to Gram-positive enhancer matrix (GEM) particles specifically. The protein expression was identified with SDS-PAGE and Western blotting, and then purified with GEM particles. Five-week old female mice were randomly divided into six groups and all the immunization was developed according to subcutaneous injection. Mice in the first three groups were injected with 50 μg/dose GEM-BT1B, GEM-BT2B and GEM-B (T1BT2) 4B, respectively. Mice in the fourth group were immunized with commercial peptide vaccine as positive control. The fifth group vaccinated with host E. coli transformed with pQZ-PA fulfilled as negative control. Mice in the last group injected with sterile PBS served as blank control. The humoral immunity of recombinant protein vaccine was evaluated with peptide-specific antibody and LPB antibody. The cellular immunity was evaluated with lymphocyte proliferation test and cytokine expression detection. SDS-PAGE and Western blotting showed that the most part of soluble target fusion protein have been purified and displayed on GEM particles. Vaccine GEM-B (T1BT2) 4B stimulated mice produce not only higher level of specific antibody against peptide and Foot-and-mouth disease virus specific liquid phase blocking antibody, but also more vigorous spleen lymph proliferation and higher levels of Th1 type cytokines. To summarize, vaccine of GEM-B (T1BT2) 4B possessed good immunogenicity and opened a new way for further Foot-and-mouth disease virus subunit vaccine design.

Immunomodulatory properties of titanium dioxide nanostructural materials.

OBJECTIVES:Although titanium dioxide (TiO2) nanostructural materials have been widely used in Biology and Medicine, very little is known about immunomodulation mechanism of these materials. Objectives of this study are to investigate in vitro immunomodulatory effects of TiO2. Immunosuppressant may lower immune responses and are helpful for the treatment of graft versus host diseases and autoimmune disorders.MATERIALS AND METHODS:In this study, we used H2Ti3O7 titanium dioxide nanotubes (TNT) nanotubes along with commercial TiO2 nanoparticles (TNP) and TiO2 fine particles (TFP). We investigated the in vitro immunomodulatory effects of TNP, TNT, and TFP using mixed lymphocyte reaction (MLR). Suppression was studied by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cytokine profile was measured by enzyme-linked immunosorbent assay (ELISA).RESULTS AND CONCLUSIONS:The results from this study illustrated that the TiO2 nanostructural materials strongly suppressed splenocytes proliferation in MLR. For TNP and TNT, at 50 μg/ml suppression of 20%–25% and 30%–35%, respectively, and for TFP at 100 μg/ml suppression was 25%–30% was observed. Suppression of splenocytes proliferation in the presence of TNP, TNT, and TFP demonstrated that these nanostructural materials probably block T-cell-mediated responses in vitro. Our ELISA results confirmed that significantly lower levels of Th1 type cytokines (interleukin-2, interferon-γ) in the 48 h MLR culture supernatants. Our data suggest that TiO2 nanostructural materials suppress splenocytes proliferation by suppressing Th1 cytokines.

Tailoring the Immune Microenvironment of Dendritic Cells by Targeting C - type Lectin Receptor

Background: The C-type lectin receptor (CLR) expressed by DCs participates in the recognition and capture of various glycosylated self-antigens and pathogens. Understanding the diversity of the CLR expressed by DCs, as well as their role in maintaining the balance between Th1-type and Th2-type cytokines would promote the understanding of the pathogenesis of many diseases including preeclampsia (PE). Methods: DCs were isolated from the placentae of healthy women who underwent normal pregnancies and infected with a CLR lentiviral (LV) vector for gene overexpression or small interfering RNA (siRNA) knockdown. DCs were cocultured with T-cells and EVCTs, and five groups were established as follows: Group 1 - DCs from healthy women who underwent normal pregnancies, Group 2 - DCs from women with preeclampsia (PE), Group 3 - DCs infected with empty LV vectors, Group 4 - DCs infected with a CLR LV vector for gene overexpression, and Group 5 - DCs infected with a CLR LV vector for siRNA knockdown. The levels of Th1- and Th2-type cytokines were measured in all groups. Results: The levels of Th1-type cytokines were significantly higher in women with PE than in those with normal pregnancies (P < 0.05). Among these five groups, the Th1/Th2 ratio of Group 5 was highest (P < 0.05). There was no difference in the Th1/Th2 ratio between Groups 1 and 3. Conclusions: There was a Th1/Th2 imbalance in women with PE displaying Th1-type immunity. CLR-overexpressing DCs showed a diminished capacity to polarize naive T-cells into Th1 effector cells. The impaired Th1 response in DCs was rescued by CLR siRNA knockdown. In conclusion, DCs may affect the production of cytokines and the migration of T-cells through CLR-mediated signaling pathways during pregnancy. Key words: C-type Lectin Receptor; Dendritic Cell; Gene Overexpression; Small Interfering RNA; T Helper 1/T Helper 2 Cytokines

Increased Serum Levels of Th2-type Cytokines and Eotaxin in Fibrillar-type Dermatitis Herpetiformis.

Increased Serum Levels of Th2-type Cytokines and Eotaxin in Fibrillar-type Dermatitis Herpetiformis.

Clinical Significance of the Balanceshift of Th1 and Th2 Type Cytokines in Patients with Primary Immune Thrombocytopenic Purpura Detected by Cytometric Bead Array

To investigate the levels of Th1/Th2 cytokines in peripheral blood of patients with primary immune thrombocytopenic purpura(ITP) before and after treatment and their clinical significance. Ninety-eight cases of ITP were treated with glucocorticoid(GC), then were divided into 2 groups: effectively treated group and uneffectively treated group according to efficacy of treatment, 40 healthy persons confirmed by health examination were selected and enrolled in control group. The levels of Th1 cytokines(IFN-γ,TNFα,IL-2) and Th2 cytokines(IL-4,IL-5,IL-10) were detected by cytometric bead array before and at 4 weeks, 3 and 6 months after treatment and the relationship among detected indexes was analyzed. Before treatment with glucocorticoid, the levels of Th1 type cytokines were in 98 patients with ITP were higher and the levels of Th2 type cytokines were lower, compared with the healthy controls(P<0.05). The IL-2/IL-4 ratio was significantly higher than that of healthy controls(P<0.05). After treatment, the levels of Th1 type cytokines in effectively treated group were significantly decreased and the levels of Th2 type cytokines were significantly increased, compared with level before treatment(P<0.05). The IL-2/IL-4 ratio was significantly decreased after treatment for 6 months, compared with that before treatment(1.05±0.43 vs 2.53±0.72)(P<0.05), but the level of Th1 or Th2 type cytokines did not obviously changed. Peripheral blood Th1 and Th2 cells express abnormally in ITP patients, ITP is a Th1 dominated disease; the change of IL-2/IL-4 ratio before and after treatment correlated with the prognosis of ITP patients, displaying clinical significance for ITP individual therapy.

Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice

Background: Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein. Methods:Scgb3a2-null (Scgb3a2^-/-) mice were subjected to nasal inhalation of Dermatophagoides pteronyssinus extract for 5 days/week for 5 consecutive weeks; control mice received nasal inhalation of saline as a comparator. Airway inflammation was assessed by histological analysis, the number of inflammatory cells and various Th2-type cytokine levels in the lungs and bronchoalveolar lavage fluids by qRT-PCR and ELISA, respectively. Results: Exacerbated inflammation was found in the airway of Scgb3a2^-/- mice subjected to house dust mite (HDM)-induced allergic airway inflammation compared with saline-treated control groups. All the inflammation end points were increased in the Scgb3a2^-/- mice. The Ccr4 and Ccl17 mRNA levels were higher in HDM-treated lungs of Scgb3a2^-/- mice than wild-type mice or saline-treated Scgb3a2^-/- mice, whereas no changes were observed for Ccr3 and Ccl11 mRNA levels. Conclusions: These results demonstrate that SCGB3A2 has an anti-inflammatory activity in the HDM-induced allergic airway inflammation model, in which SCGB3A2 may modulate the CCR4-CCL17 pathway. SCGB3A2 may provide a useful tool to treat allergic airway inflammation, and further studies on the levels and function of SCGB3A2 in asthmatic patients are warranted.

241 Increased serum levels of Th2-type cytokines and eotaxin in fibrillary-type dermatitis herpetiformis

241 Increased serum levels of Th2-type cytokines and eotaxin in fibrillary-type dermatitis herpetiformis

Esculentoside A Attenuates Allergic Airway Inflammation via Activation of the Nrf-2 Pathway

Background: The role of airway inflammation and inflammation-induced oxidative stress in the pathogenesis and progression of chronic inflammatory airway diseases has received increasing attention in recent years. We investigated the potential anti-inflammatory and antioxidative effects of esculentoside A (EsA), a saponin isolated from the Chinese herb Phytolacca esculenta, in comparison to dexamethasone, a potent corticosteroid, in a murine model of allergic asthma. Methods: EsA was added to cultures of A549 cells at different concentrations or for different lengths of time, and nuclear factor erythroid 2-related factor 2 (Nrf-2) translocation and heme oxygenase 1 expression were monitored. Mice treated with or without EsA and Nrf-2 siRNA were sensitized and challenged with ovalbumin (OVA) and developed airway inflammation and oxidative lung damage. The Th2-type cytokine levels and inflammatory cells in bronchoalveolar lavage fluid (BALF) and the serum immunoglobulin production and adhesion molecule expression in the lung tissues were measured. The activities of related antioxidases and glutathione were measured using assay kits. Results: EsA enhanced nuclear Nrf-2 translocation in both A549 cells and the lungs of OVA-challenged mice. Airway inflammation induced by OVA was reduced. Additionally, EsA increased mRNA expression of antioxidant enzymes regulated by Nrf-2, leading to a reduction in Th2 cytokines and the expression of adhesion molecule mRNA in the BALF and lung tissues. Inhibition of Nrf-2 by siRNA abrogated the regulatory effects of EsA on inflammation and oxidant stress. Conclusions: This is the first study to illustrate that EsA acts as a novel Nrf-2 activator, which modulates the oxidative stress pathway to improve lung injury and ameliorate the development of airway inflammation.

Soshiho-tang water extract inhibits ovalbumin-induced airway inflammation via the regulation of heme oxygenase-1.

BackgroundSoshiho-tang, known as Xio-hai-Hu-Tang in Chinese and Sho-Saiko-to in Japanese, has been widely used as a therapeutic agent. Its pharmacological effects include anti-inflammatory, antioxidant, antihepatic fibrosis, antitumor and immunomodulating activities. However, little is known regarding its effects on allergic asthma. Therefore, the aim of the present study was to investigate whether the Soshiho-tang water extract (SSTW) has antiasthmatic effects on airway inflammation in an ovalbumin (OVA)-induced mouse model.MethodsBALB/c mice were used as a model of asthma after induction by sensitization and challenge with OVA. We measured change in eosinophils, other inflammatory cells, and T helper 2 (Th2)-type cytokines, such as interleukin (IL)-4, IL-5, IL-13, IL-17, IL-33, and chemokine (eotaxin) in bronchoalveolar lavage fluid (BALF), presence of total and OVA-specific immunoglobulin (Ig)E in plasma, and expression of mucus production and heme oxygenase (HO)-1 protein in lung tissue.ResultsOur results show that SSTW had a suppressive effect on eosinophil influx into BALF and decreased the levels of Th2-type cytokines. Moreover, SSTW exhibited a marked decrease in mucus hypersecretion, total and OVA-specific IgE levels, and significantly induced HO-1 protein expression.ConclusionsThese results suggest that SSTW may be used as a valuable therapeutic agent for treating various inflammatory diseases including allergic asthma.

Efficacy and immunogenicity of recombinant swinepox virus expressing the A epitope of the TGEV S protein

To explore the possibility of developing a vaccine against transmissible gastroenteritis virus (TGEV) infection, a recombinant swinepox virus (rSPV-SA) expressing a TGEV protective antigen has been constructed. Immune responses and protection efficacy of the vaccination vector were assessed in both mice and pig models. An indirect ELISA assay suggested that when mice were vaccinated with rSPV-SA, the level of IgG against TGEV was enhanced dramatically. The cytokine assays were employed and the results indicated that both the Th1-type and Th2-type cytokine levels raised after vaccination with rSPV-SA in mice models. Results from the passive immunity protection test of new born piglets demonstrated that the recombinant live-vector vaccine, rSPV-SA, could 100% protect piglets from the SPV infection, and there was no significant clinical symptom in the rSPV-SA treatment group during this experiment. The data suggest that the novel recombinant swinepox virus is a potential vaccine against TGEV infection.

IM-14 * IMMUNOLOGIC TARGETING OF MEDULLOBLASTOMA SUBTYPES USING DEVELOPMENTALLY REGULATED ANTIGENS

INTRODUCTION: Medulloblastoma (MB) remains incurable in one third of patients despite aggressive multi-modality standard therapies. Immunotherapy represents a promising strategy by specifically targeting cancer cells. To date, there have been no successful immunologic applications targeting MB. Evidence from integrated genomic studies suggests MB subtypes arise from deregulation of pathways affecting proliferation of progenitor populations within the developing cerebellum. Using total embryonic RNA as a source of tumor rejection antigens is attractive because it can be delivered as a single vaccine, target both known and unknown fetal proteins, and be refined to preferentially treat distinct MB subtypes. METHODS: We have created two transplantable, syngeneic animal MB models recapitulating human SHH and Group 3 variants to investigate the immunologic targeting of different MB subtypes. We generated T cells specific to the developing mouse cerebellum (P5) and tested their reactivity to target cells pulsed with total RNA from two MB subtypes and the normal brain. Immune responses were evaluated by measuring cytokine secretion following re-stimulation of activated T cells with both normal and tumor cell targets. In vivo antitumor efficacy was also tested in survival studies of intracranial tumor-bearing animals. RESULTS: We generated T cells specific to the developing cerebellum in vitro, confirming the immunogenicity of developmentally regulated antigens. Additionally, we have shown that developmental antigen-specific T cells produce high levels of Th1-type cytokines in response to tumor cells of two immunologically distinct subtypes of MB. Interestingly, developmental antigen specific T cells do not show cross reactivity with the normal brain or subsequent stages of the developing brain after P5. Targeting developmental antigens also conferred a significant survival benefit in a treatment model of Group 3 tumor bearing animals and 60% survivors in SHH tumor bearing animals. CONCLUSIONS: Developmental antigens can safely target multiple MB subtypes with equal effectiveness compared to previously established total tumor strategies.

Clinical Influence of Different Intracanal Medications on Th1-type and Th2-type Cytokine Responses in Apical Periodontitis

IntroductionThis clinical study assessed the influence of different intracanal medications on Th1-type and Th2-type cytokine responses in apical periodontitis and monitored the levels of bacteria from primarily infection during endodontic procedures. MethodsThirty primarily infected teeth were randomly divided into 3 groups according to the medication selected: chlorhexidine (CHX), 2% CHX gel; Ca(OH)2/SSL, Ca(OH)2 + SSL; and Ca(OH)2/CHX, Ca(OH)2 + 2% CHX gel (all, n = 10). Bacterial sample was collected from root canals, and the interstitial fluid was sampled from lesions. Culture techniques were used to determine bacterial counts (colony-forming units/mL). Th1 (tumor necrosis factor-α, interferon-γ, and interleukin [IL]-2) and Th2 cytokines (IL-4, IL-5, and IL-13) were measured by enzyme-linked immunosorbent assay. ResultsAll intracanal medication protocols were effective in reducing the bacterial load from root canals (all P < .05) and lowering the levels of Th1-type cytokines in apical lesions (all P < .05), with no differences between them (P > .05). Both Ca(OH)2 treatment protocols significantly increased the levels of Th2-type cytokines (P < .05), with no differences between them (P > .05). Thus, chlorhexidine medication showed the lowest effectiveness in increasing the levels of Th2-type cytokine. After treatment, regardless of the type of medication, the linear regression analysis indicated the down-regulation of Th2-type cytokines by Th1-type cytokines. ConclusionsAll intracanal medication protocols were effective in reducing bacterial load and lowering the levels of Th1-type cytokines. Thus, the use of Ca(OH)2 medications contributed to the increase in the Th2-type cytokine response in apical periodontitis.

IT-25 * DEVELOPMENTALLY REGULATED ANTIGENS FOR IMMUNOLOGIC TARGETING OF MEDULLOBLASTOMA SUBTYPES

INTRODUCTION: Medulloblastoma (MB) remains incurable in one third of patients despite aggressive multi-modality standard therapies. Immunotherapy presents a promising alternative by specifically targeting cancer cells. To date, there have been no successful immunologic applications targeting MB. Emerging evidence from integrated genomic studies has suggested MB variants arise from deregulation of pathways affecting proliferation of progenitor cell populations within the developing cerebellum. Using total embryonic RNA as a source of tumor rejection antigens is attractive because it can be delivered as a single vaccine, target both known and unknown fetal proteins, and can be refined to preferentially treat distinct MB subtypes. METHODS: We have created two transplantable, syngeneic animal MB models recapitulating human SHH and Group 3 variants to investigate the immunologic targeting of different MB subtypes. We generated T cells specific to the developing mouse cerebellum (P5) and tested their reactivity to target cells pulsed with total RNA from two MB subtypes and the normal brain. Immune responses were evaluated by measuring cytokine secretion following re-stimulation of activated T cells with both normal and tumor cell targets. In vivo antitumor efficacy was also tested in survival studies of intracranial tumor-bearing animals. RESULTS: We generated T cells specific to the developing cerebellum in vitro, confirming the immunogenicity of developmentally regulated antigens. Additionally, we have shown that developmental antigen-specific T cells produce high levels of Th1-type cytokines in response to tumor cells of two immunologically distinct subtypes of MB. Interestingly, developmental antigen specific T cells do not show cross reactivity with the normal brain or subsequent stages of the developing brain after P5. Targeting developmental antigens also conferred a significant survival benefit in a treatment model of Group 3 tumor bearing animals. CONCLUSIONS: Developmental antigens can safely target multiple MB subtypes with equal effectiveness compared to previously established total tumor strategies.

The Immunoregulatory Role of Cytokines in Congestive Heart Failure

Background: Cytokines have been shown to be associated with heart failure and to have multiple biological effects that can lead to left ventricular dysfunction, pulmonaryedema, and left ventricular remodeling. However, the effects of different cytokines, separately and in combination have not been fully determined. We aim to evaluate the levels of both pro-inflammatory and anti-inflammatory cytokines in patients with congestive heart failure (CHF), as well as in patients with coronary artery disease (CAD) and compare them to levels in normal controls (individuals without CHF or CAD) as to suggest their possible etiologic role. Methods and results: In our study, the serum levels of IL-6, IL-10, IL-1β, IL-2 and TNF-α were measured in 19 patients with CHF, 18 patients with CAD without CHF and 8 controls, using immunoassays. There was a significant increase in the serum levels of IL-6, IL1-β, IL-10 and TNFα in the CHF group, and of IL-6, IL-1β and TNFα in the CAD group, compared with controls. Patients with CHF had significantly higher levels of anti-inflammatory cytokines IL-6 and IL-10 and lower levels of pro-inflammatory cytokines IL-2 compared when compared patients with CAD, emphasizing the different pathophysiologic mechanisms for these conditions. Conclusion: Our studies suggest that patients with CHF had higher levels of Th2-type cytokines than patients with CAD, suggesting their role in the development of heart failure. Further studies are required to elucidate the role of cytokines in heart failure, and to understand the biological effects of cytokines and their role in the development of CHF. This may lead to development of new treatments modalities targeting their effects.

The Beneficial Effect of Total Glucosides of Paeony on Psoriatic Arthritis Links to Circulating Tregs and Th1 Cell Function

Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony. It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis. However, data of TGP effect on psoriatic arthritis (PsA) is still scarce. In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12. Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-γ and TNF-α), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined. Six patients (32%) exhibited ≥25% decrease of DAS28 (responders). Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels. Serum IL-6 also showed a significant decline in responders. Non-responders lacked these sequential alterations. Thus, TGP merits further consideration as a promising therapeutic option for PsA. The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA.

Topical application of Taglisodog-eum inhibits the development of experimental atopic dermatitis

Aim of studyTaglisodog-eum (▪, Tuo Li Xiao Du Yin), a standardized herbal formula, has been widely used to modulate diverse carbuncles in oriental medicine. However, it is still unclear whether Taglisodog-eum (TSE) can exert a beneficial role in dermatological disease. In this study, we examined the effect of topical application of TSE on experimental atopic dermatitis (AD) and elucidated its action mechanism. Materials and methodsTo test the effect of TSE treatment on IgE production in vitro, U266B1 cells and primary CD19+ B cells isolated from AD-induced mice were treated with TSE under LPS/IL-4 stimulation and then IgE level in the culture supernatant was measured by ELISA. To evaluate the effect of TSE treatment on the production of AD related pathogenic cytokines, CD4+ T cells isolated from AD-induced mice were treated with TSE under PMA/ionomycin stimulation, then the level of cytokine expression was analyzed by quantitative RT-PCR and ELISA. The effects of TSE on the NFκB promoter activity in T cells and on the expression level of Aicda (activation-induced cytidine deaminase) in B cells were examined. To further examine the in vivo efficacy of TSE on AD progression, TSE was topically applied to ears of mice with atopic dermatitis induced by painting of DNCB and house dust mite extract. AD Progression was estimated by following criteria: (a) ear thickness, clinical score, (b) serum total IgE and mite specific IgE level by ELISA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and draining lymph node CD4+ T cells by quantitative real time PCR and ELISA. ResultsTreatment of TSE to the U266B1 cell line and primary CD19+ B cells isolated from AD-induced mice inhibited IgE production. Treatment of TSE down-regulated the expression of several cytokines (IL-4, IL-10, IL-13, IL-17, TNF-α and IFN-γ) in CD4+ T cells isolated from AD-induced mice. Topical application of TSE on the ears of AD-induced mice decreased the severity and progression of disease by reducing ear thickness, clinical scores including dryness, edema. TSE treatment reduced the infiltration of lymphocytes to the inflamed site analyzed by histological evaluation. TSE treatment also decreased serum IgE level and expression of AD-associated pathogenic cytokines (IL-4, IL-5 and IL-13) in total ear cells and dLN CD4+ T cells by inhibiting the translocation of NFκB into nucleus. ConclusionsOur study indicates that protective effect of Taglisodog-eum (TSE) in experimental atopic dermatitis is mediated by inhibiting IgE production and the levels of Th2 type cytokines, suggesting the beneficial effect of TSE on modulating atopic dermatitis.