Apelin receptor antagonist boosts dendritic cell vaccine efficacy in controlling angiogenic, metastatic and apoptotic-related factors in 4T1 breast tumor-bearing mice.

Apelin/APJ axis plays a critical role in cancer progression, thus its targeting inhibits tumor growth. However, blocking of Apelin/APJ axis in combination with immunotherapeutic approaches may be more effective. This study aimed to investigate the effects of APJ antagonist ML221 in combination with a DC vaccine on angiogenic, metastatic and apoptotic-related factors in a breast cancer (BC) model. Four groups of female BALB/c mice with 4T1-induced BC were treated with PBS, APJ antagonist ML221, DC vaccine, and "ML221 + DC vaccine". After completion of the treatment, the mice were sacrificed and the serum levels of IL-9 and IL-35 as well as the mRNA expression of angiogenesis (including VEGF, FGF-2, and TGF-ß), metastasis (including MMP-2, MMP-9, CXCR4) and apoptosis-related markers (Bcl-2, Bax, Caspase-3) in tumor tissues were determined using ELISA and real-time PCR, respectively. Angiogenesis was also evaluated by co-immunostaining of tumor tissues with CD31 and DAPI. Primary tumor metastasis to the liver was analyzed using hematoxylin-eosin staining. The efficiency of combination therapy with "ML221 + DC vaccine" was remarkably higher than single therapies in preventing liver metastasis compared to the control group. In comparison with the control group, combination therapy could significantly reduce the expression of MMP-2, MMP-9, CXCR4, VEGF, FGF-2, and TGF-ß in tumor tissues (P < 0.05). It also decreased the serum level of IL-9 and IL-35 compared with the control group (P < 0.0001). Moreover, vascular density and vessel diameter were significantly reduced in the combination therapy group compared with the control group (P < 0.0001). Overall, our findings demonstrate that combination therapy using a blocker of the apelin/APJ axis and DC vaccine can be considered a promising therapeutic program in cancers.

Down-regulation of transforming growth factor-beta and interleukin-6 serum levels in the idiopathic chronic obstructive pulmonary disease.

BACKGROUND: Idiopathic chronic obstructive pulmonary disease (ICOPD) is a prevalent human disease. The etiology of the disease is yet to be clarified. The main aim of this project was to explore serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) in the ICOPD patients in comparison to healthy controls. METHODS: In this cross-sectional study, serum levels of IL-6, TNF-α and TGF-ß were evaluated in the 70 non-smoker ICOPD patients and 70 sex and age matched controls, using ELISA technique by the commercial kits from Karmania Pars Gene Company. Analysis of data was performed by parametric independent and Pearson correlation test. RESULTS: Serum levels of IL-6 and TGF-ß, but not TNF-α, were significantly decreased in the ICOPD patients in comparison to controls. Serum levels of IL-6, TNF-α and TGF-ß were not altered in the ICOPD male in comparison to female and also in mild when compared to moderate ICOPD patients. CONCLUSIONS: Down-regulation of TGF-ß may be the main risk factor for deterioration of inflammation in the ICOPD patients. Decreased IL-6 may be related to the idiopathic type of COPD.

Role of maternal interleukin-8 (IL-8) in normal-term birth in the human.

Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor ß (TGF-ß) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-ß were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-ß and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-ß production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.

Interleukin-6 and Tumor Growth Factor-ß are Risk Factors for Idiopathic Epistaxis.

OBJECTIVE: To evaluate the serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-ß, endothelin, and immunoglobulin (Ig)E in patients with idiopathic epistaxis, compared with healthy control individuals. METHODS: Serum levels of IL-6, IL-8, TNF-α, TGF-ß, endothelin, and IgE were evaluated in 110 patients with idiopathic epistaxis and 100 healthy controls using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Serum levels of IL-6 (P <.001) and TGF-ß (P = .001) were significantly increased in patients with idiopathic epistaxis, compared with controls. TNF-α serum levels were significantly increased in male patients, compared with female patients (P = .053). We observed decreased antihistamine levels and increased expression of TGF-ß (P = .02) and TNF-α (P = .02), respectively. CONCLUSIONS: IL-6 and TGF-ß appear to participate in the pathogenesis of idiopathic epistaxis. TNF-α may be considered a risk factor for male patients in developing epistaxis. Antihistamines may inhibit angiogenesis by decreasing expression of TGF-ß and increasing expression of TNF-α.

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

INTRODUCTION: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, and endothelin (ET)-1). MATERIAL AND METHODS: Serum levels of IL-6, IL-8, TGF-ß, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12. RESULTS: Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-ß. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients. DISCUSSION: Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients.

SPECIFIC SERUM IMMUNOGLOBULIN G AGAINST CHLAMYDIA PNEUMONIAE IN HEALTHY CHILDREN AND ADULTS IN SOUTH-EAST OF IRAN.

BACKGROUND: Chlamydia pneumoniae (C. pneumonia) is an obligate intracellular bacterium and recognized as a risk factor for several diseases such as asthma, atherosclerosis and arthritis. The aim of this study was to determine the seroprevalence of C. pneumonia in healthy subjects in different age groups. METHODS: The serum levels of anti C. pneumonia IgG were measured by using of ELISA. RESULTS: Totally, 630 subjects (164 children and 466 adults) were included into study. The seroprevalence and the mean titer of anti C. pneumonia antibody were 11.3% and 14.48?2.18 RU/mL; at age 510 years, 15% and 17.47 +/- 2.40 RU/mL at age 11-20 years, 21% and 25.15 +/- 4.56 RU/mL at age 21-30 years group, 40% and 53.77 +/- 6.40 RU/mL at age 31-40 years, 94% and 146.41 +/- 8.95 RU/mL at age 41-50 years, 98% and 153.59 +/- 10.38 RU/mL at age 51-60 years, 96% and 138.80 +/- 12.78 RU/mL at age 61-70 years, respectively. The differences of the seroprevalence and the mean titer of anti C. pneumonia antibody between age groups were significant (p<0.0001). The sero-prevalence and the mean titer of anti C. pneumonia antibody were 11.6% and 14.33 +/- 1.49 RU/mL in children and 65.5% and 97.40 +/- 4.46 RU/mL in adults. The seroprevalence and the mean titer of anti C. pneumonia antibody were significantly higher in adults in comparison with those in children (p<0.0001). CONCLUSION: These findings showed that the sero- prevalence and titer of anti C. pneumonia IgG were increased with advanced ages and were higher in adults as compared to children.

Levels of Transforming Growth Factor-Beta After Immunization of Mice With in vivo prepared Toxoplasma gondii Excretory/Secretory Proteins.

BACKGROUND: Zoonotic parasite Toxoplasma gondii has a high prevalence in human populations. A suitable vaccine for animals can stop the transmission of infection between animal and human. OBJECTIVES: The aim of this study was to evaluate in vivo prepared excretory/secretory antigens (E/SA) as a potential candidate for immunization against the parasite and its effect on the production of transforming growth factor-beta (TGF-ß). MATERIALS AND METHODS: Toxoplasma gondii tachyzoites were inoculated in the peritoneal cavity of mice and E/SA was harvested and used in animal immunization with and without adjuvant. Serum levels of anti-E/SA antibodies and TGF-ß were measured in days 0, 3, 7, 14, 28 and 56 after immunization using ELISA technique. The measurements were statistically analyzed. RESULTS: Our results showed that the serum levels of anti-E/SA immunoglobulins significantly increased in all of the immunized groups. The differences of the serum levels of TGF-ß between the groups were statistically significant at days 28 and 56 after immunization with E/SA. CONCLUSIONS: Based on our study, in vivo prepared E/SA may be considered as a good candidate for animal immunization.

The persistence of anti-HBs antibody and anamnestic response 20 years after primary vaccination with recombinant hepatitis B vaccine at infancy.

Hepatitis B (HB) vaccine induces protective levels of antibody response (anti-HBs≥10 mIU/mL) in 90-99% of vaccinees. The levels of anti-HBs antibody decline after vaccination. The aim of this study was to evaluate the persistence of anti-HBs antibodies and immunologic memory in healthy adults at 20 years after primary vaccination with recombinant HB vaccine. Blood samples were collected from 300 adults at 20 years after primary HB vaccination and their sera were tested for anti-HBs antibody by ELISA technique. A single booster dose of HB vaccine was administered to a total of 138 subjects, whose anti-HBs antibody titer was <10 mIU/mL. The sera of subjects were re-tested for the anti-HBs antibody levels at 4 weeks after booster vaccination. At 20 years after primary vaccination 37.0% of participants had protective levels of antibody with geometric mean titer (GMT) of 55.44±77.01 mIU/mL. After booster vaccination, 97.1% of vaccinees developed protective levels of antibody and the GMT rose from 2.35±6.49 mIU/mL to 176.28±161.78 mIU/mL. 125/138 (90.6%) of re-vaccinated subjects also showed an anamnestic response to booster vaccination. At 20 years after primary vaccination with HB vaccine, low proportion of the subjects had protective levels of antibody. However, the majority of the re-vaccinated subjects developed protective levels of anti-HBs and showed an anamnestic response after booster vaccination. Additional follow-up studies are necessary to determine the duration of immunological memory.

Interleukin-10 Serum Levels after Vaccination with In Vivo Prepared Toxoplasma gondii Excreted/Secreted Antigens.

OBJECTIVES: Toxoplasma gondii is a worldwide prevalent zoonotic parasite which causes toxoplasmosis. An appropriate vaccine for animals could interrupt the circle between animals and humans. Our previous study showed that excreted/secreted antigens (E/SA), derived from the peritoneum of mice infected with T. gondii tachyzoites could be considered as a good candidate for animal vaccination. Interleukin-10 (IL-10) inhibits proliferation of B and T lymphocytes and induces homeostasis in immune system responses. However, since IL-10 has also been shown to suppress the killing of T. gondii by human macrophages, the aim of this study was to evaluate IL-10 serum levels after vaccination with T. gondii E/SA prepared in vivo. METHODS: T. gondii tachyzoites were inoculated in the peritoneum of mice and harvested E/SA were used as a vaccine, with and without adjuvant, in T. gondii infected and un-infected mice. IL-10 serum levels were evaluated using the ELISA technique. RESULTS: The data showed that although serum levels of IL-10 were not changed at the early phases, they were elevated at the end phases of vaccination with T. gondii E/SA. CONCLUSION: Based on these and our previous results, it can be concluded that in vivo prepared T. gondii E/SA could be considered as a good candidate for animal vaccination.

CCR5 Δ 32 mutation is not prevalent in Iranians with chronic HBV infection.

CCR5 is an important chemokine receptor involved in the recruitment of specific anti-viral immune cells (e.g., NK cells and T cytotoxic cells) to the liver. Previous studies indicated that the Δ 32 mutation in CCR5 gene led to inactivation of CCR5. Several conflicting studies have suggested that this mutation may be associated with either recovery or persistence of HBV infection. The main purpose of this study was to compare the frequency of the Δ 32 mutation within the CCR5 gene in a group of patients infected chronically with HBV with healthy individuals from South-East of Iran. Sixty patients with chronic HBV infection as well as 300 age-, and sex-match healthy individuals were enrolled in this study. Gap-PCR was applied to determine the frequency of CCR5 Δ 32 mutation in both groups. The results demonstrated that none of the patients infected with HBV carried the CCR5 Δ 32 mutation while, 3 (1%) of the healthy individuals were found to be heterozygotic for this mutation. The CCR5 Δ 32 mutation is not a prevalent mutation in either the patients infected chronically with HBV or their health counterparts in the South-East region of Iran. This may be attributed to either different genetic settings of the investigated population or lack of any significant correlation between this mutation and HBV pathogenicity.

Circulating interleukin-27 levels in Helicobacter pylori-infected patients with gastric or duodenal ulcers, independent of the bacterial cytotoxin-associated gene A virulence factor.

OBJECTIVE: The aim was to evaluate the interleukin (IL)-27 levels in Helicobacter pylori (H. pylori)-infected patients with gastric ulcer (GU) or duodenal ulcer (DU) and to determine its association with H. pylori virulence factor cytotoxin-associated gene A (CagA). METHODS: In all, 127 H. pylori infected patients (including 96 DU patients, of whom 61 were anti-CagA(+) and 35 were anti-CagA(-)) and 31 GU patients (of whom 15 were anti-CagA(+) and 16 were anti-CagA(-)), 60 asymptomatic (AS) carriers (of whom 30 were anti-CagA(+) and 30 were anti-CagA(-)) and 30 healthy H. pylori-negative participants (as a control) were enrolled in the study. Serum concentrations of IL-27 were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean levels of IL-27 in the GU (44.26 ± 7.12 pg/mL) and DU patients (40.84 ± 3.90 pg/mL) was significantly higher than those observed in the AS carriers (22.06 ± 1.90 pg/mL, P < 0.001) and the control group (18.12 ± 1.68 pg/mL, P < 0.001 and P < 0.002, respectively). In the GU, DU and AS groups the levels of IL-27 in anti-CagA(+) participants were not significantly differ from that in the anti-CagA(-) participants. CONCLUSIONS: These results showed that the mean concentration of IL-27 in H. pylori-infected peptic ulcer (PU) patients was higher than in AS carriers and the healthy control group. The serum concentrations of IL-27 were not affected by the CagA factor.

High serum levels of rheumatoid factor and anti-phosphatidylserine antibody in patients with ischemic heart disease.

BACKGROUND: Immunopathological and inflammatory processes play important roles in the initiation and development of Ischemic Heart Disease (IHD). OBJECTIVE: The aim of this study was to evaluate the serum levels of several autoantibodies including rheumatoid factor (RF), anti-nuclear antibodies (ANA), anti-small nuclear ribonucleoprotein (anti-Sm), anti-phosphatidylserine (anti-PS) and anti-cardiolipin (anti-CL) antibodies in patients with IHD. METHODS: A total of 120 patients with IHD with acute myocardial infarction (AMI; n=60) or unstable angina (UA; n=60) and 60 sex- and age-matched healthy subjects were enrolled in this study. Serum samples of participants were tested for the ANA, anti-Sm, anti-PS and anti-CL antibodies by ELISA. Serum level of RF was measured by a turbidometric method. RESULTS: The mean serum levels of RF and anti-PS antibodies in AMI group and UA group were significantly higher than those observed in the control group (p<0.0001). The mean serum levels of RF and anti-PS antibodies in AMI patients were significantly higher than the UA group (p<0.01 and p<0.001, respectively). The mean serum levels of RF in men with AMI or UA diseases were significantly higher as compared to healthy control men (p<0.0001 and p<0.003, respectively). The differences of the serum levels of ANA, anti-Sm and anti-CL antibodies were not significant between AMI, UA and the control groups. There was no difference in the serum levels of RF, ANA, anti-Sm, anti-PS or anti-CL antibodies in patients with traditional risk factors, including hypertension, dyslipidemia, diabetes and smoking, and those without a certain risk factor. CONCLUSION: Higher serum levels of RF and anti-PS antibody in patients with IHD may be considered as independent risk factors for IHD.