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.

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.