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.

Cimetidine and Ibuprofen Modulate T Cell Responses in a Mouse Model of Breast Cancer.

Cimetidine and ibuprofen exhibit immunomodulatory effects as an antagonist of histamine H2 receptor, and a cyclooxygenase inhibitor, respectively. Here, the effects of cimetidine and ibuprofen on some effector T cell-related parameters were investigated using a breast cancer (BC) model. BC was established in Balb/c mice using the 4T1 cell line. On day 10 after tumor induction, the BC-bearing mice were classified into four groups and treated with PBS, cimetidine (20 mg/kg), ibuprofen (20 mg/kg) or a combination of "cimetidine + ibuprofen" via intraperitoneal injection (daily from days 11 to 30). The mice were sacrificed on day 31 and the frequency of splenic Th1 and Treg cells, plasma IFN-γ and TGF-ß levels, and intra-tumoral T-bet, GATA3, FOXP3 and RORγt expressions were detected using flowcytometry, ELISA and real-time-PCR, respectively. In untreated cancerous mice, the percentage of splenic Th1 cells and plasma IFN-γ levels were lower (P<0.003 and P<0.01, respectively), whereas the percentage of splenic Treg cells and plasma TGF-ß levels were higher than in healthy mice (P<0.04 and P<0.005, respectively). Treatment of BC-bearing mice with cimetidine, ibuprofen or both drugs promoted the frequency of Th1 cells (P<0.05, P<0.007 and P<0.005, respectively) as well as IFN-γ levels (P<0.004, P<0.0001 and P<0.03, respectively), while reduced the frequencies of Treg cells (P<0.02, P<0.03 and P<0.01, respectively), TGF-ß levels (P<0.006, P<0.02 and P<0.002, respectively), intra-tumoral expression of FOXP3 (P<0.006, P<0.005 and P<0.005, respectively), and intra-tumoral expression of RORγt (P<0.04, P<0.03 and P<0.05, respectively) compared with untreated BC mice. The "cimetidine + ibuprofen"-treated mice displayed greater T-bet expression than the un-treated mice (P<0.006). Cimetidine and/or ibuprofen-treated BC-bearing mice exhibited reduced intra-tumoral expression of GATA3 compared with the untreated BC mice, but the differences were not significant. Cimetidine and ibuprofen correct some effector T cell-related parameters in cancerous mice. Immunotherapeutic potentials cimetidine and ibuprofen in cancers need investigations.

Modulatory Effects of Metformin Alone and in Combination with Cimetidine and Ibuprofen on T Cell-related Parameters in a Breast Cancer Model.

Metformin, cimetidine, and ibuprofen separately exhibit immunomodulatory and anti-tumorigenic effects. Herein, the impacts of metformin alone and in combination with cimetidine/ibuprofen on some Th1- and regulatory T (Treg) cell-related parameters were evaluated using a breast cancer (BC) model. For establishing the BC model, four groups of Balb/c mice were challenged with the carcinoma cell line. After 11-30 days post-induction, they were treated intraperitoneally (with metformin (200 mg/kg), "metformin plus cimetidine (20 mg/kg)"; "metformin plus ibuprofen (20 mg/kg)", or with all three drugs in mentioned doses. Untreated BC and without tumor mice were enrolled as control groups. On day 31, splenic Th1 and Treg cell frequencies, serum interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-ß) concentration, and intra-tumoral T-bet, TGF-ß, and forkhead box protein P3 (FOXP3) expression were measured; using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time-PCR, respectively. Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-γ concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-ß concentration, and the expression of FOXP3 and TGF-ß compared with un-treated BC mice. FOXP3 expression in the metformin-treated group was lower in mice who received combination therapy. Survival rate and body weight were increased, while tumor size and spleen index were reduced in mice treated with metformin alone and its combination with cimetidine and/or ibuprofen. No remarkable differences were found between metformin-treated mice and those who received combination therapies regarding Th1 and Treg cell percentages, TGF-ß expression, body weight, tumor size, and spleen index. The benefits of combinational therapy may be largely attributed to metformin. Immunotherapeutic potentials of metformin in cancers need further considerations.

Zingerone improves the immune responses in an animal model of breast cancer.

OBJECTIVES: The potent anti-tumorigenic effects were attributed to ginger and there are some reports regarding the anti-cancer and immunomodulatory properties ginger-derived components. This study aimed to investigate the effects of zingerone on some immune-related parameters in an animal model of breast cancer. METHODS: The breast cancer was established in female BALB/c mice using a carcinogenic 4T1 cell line. At day 10 after cancer induction, tumor-bearing mice were divided into five groups and treated intraperitoneal (daily from days 11-30) with saline or zingerone (at doses 10, 20, 50 and 100 mg/kg/day). The mice were sacrificed on day 31 and the number of splenic Th1- and Treg cells, the expression of IFN-γ and TGF-ß in the blood mononuclear cells, the antibody production against sheep red blood cell (SRBC) were determined using flow cytometry, real time-PCR and a standard hemagglutination assay, respectively. RESULTS: Zingerone at doses 50 and 100 mg/kg enhanced the number of splenic Th1 cells (p<0.03 and 0.007, respectively); at doses 10, 20, 50 and 100 mg/kg reduced the number of splenic Treg cells (p<0.02, 0.01, and 0.01, respectively), at doses 50 and 100 mg/kg enhanced the expression of IFN-γ (p<0.03), at doses 50 and 100 mg/kg reduced the expression of TGF-ß, at doses 50 mg/kg reduced the titer of anti-SRBC antibody (p<0.05). CONCLUSIONS: Zingerone improve the T cell-mediated and antibody responses in a mouse model of breast cancer. The immunotherapeutic potentials of zingerone in cancers need more considerations.

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.

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.

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.

Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients.

OBJECTIVES: H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. METHODS: A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. RESULTS: The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (p<0.05). Although, the mean serum levels of rheumatoid factor and anti-nuclear antibodies in the asymptomatic carriers group was higher than those in the control group, the difference was not statistically significant. No significant differences were observed between peptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (p<0.05). Although in female of peptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. CONCLUSION: The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection.

Lower circulating levels of chemokine CXCL10 in Helicobacter pylori-infected patients with peptic ulcer: Influence of the bacterial virulence factor CagA.

BACKGROUND AND OBJECTIVES: Alterations in CXCL10 (a Th1 chemokine) expression have been associated with various diseases. The aim of this study was to evaluate the serum CXCL10 levels in H. pylori-infected patients with peptic ulcer (PU), H. pylori-infected asymptomatic (AS) subjects and healthy H. pylori-negative subjects, and also to determine its association with bacterial virulence factor cytotoxin-associated gene A (CagA). MATERIALS AND METHODS: Serum samples from 90 H. pylori infected patients with PU (70 were anti-CagA(+), 20 were anti-CagA(-)), 65 AS carriers (40 were anti-CagA(+), 25 were anti-CagA(-)) and 30 healthy H. pylori-negative subjects (as a control group) were tested for concentrations of CXCL10 by using the ELISA method. RESULTS: The mean serum levels of CXCL10 in PU patients (96.64 ± 20.85 pg/mL) were significantly lower than those observed in AS subjects (162.16 ± 53.31 pg/mL, P < 0.01) and the control group (193.93 ± 42.14 pg/mL, P < 0.02). In the PU group, the serum levels of CXCL10 in anti-CagA(+) subjects was significantly higher in comparison to anti-CagA(-) patients (P < 0.04). CONCLUSION: These results showed that the mean concentrations of CXCL10 in H. pylori-infected-PU patients was lower than AS carriers and control group. In the PU group, the serum levels of CXCL10 were associated with bacterial factor CagA.

Helicobacter pylori seropositivity in patients with type 2 diabetes mellitus in south-east of Iran.

It has been also reported that that H. pylori infection may be responsible for some endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus and primary hyperparathyroidism. H. pylori which express cytotoxin-associated gene A (CagA) may be more virulent than those that do not. The aim was to evaluate the seroprevalence of anti-H. pylori IgG and anti-CagA  antibodies in patients with type 2 diabetes mellitus (type 2 DM) and healthy individuals from Rafsanjan city (Iran). A total of 100 patients with type 2 diabetes and 100 age-matched healthy individuals were enrolled to study. A blood sample was collected from each participant. The type 2 DM established according to the fasting blood glucose level of 126 mg/dl. The sera were tested for the presence of anti-H. pylori IgG antibodies and antibody to CagA by use of enzyme linked immunosorbent assay. The seroprevalence of anti-H. pylori antibodies in diabetic  patients (76%) was similar to that observed in healthy subjects (75%). The mean titer of anti-H. pylori IgG in healthy control group (131.63±11.68 U/ml) was significantly higher than diabetic group (54.43±4.50 U/ml; P<0.0001). The prevalence of serum anti-CagA IgG antibodies was 78.9% in infected diabetic patients and 77.3% in healthy control group with mean titer of 75.02±4.54 U/ml and 84.34±5.85 U/ml, respectively. No significant differences were observed between diabetic and healthy control groups regarding the prevalence and the mean titer of anti-CagA IgG antibodies. In the diabetic group, the seropositive rate of anti-H. pylori IgG was higher in women as compared to men, but the difference was not statistically significant. These results show that H. pylori seropositivity rate was similar in type 2 DM patients and non-diabetics control group. No association was also found between CagA-positive strains of H. pylori and type 2 DM.

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.

Association of the CagA status of Helicobacter pylori and serum levels of interleukin (IL)-17 and IL-23 in duodenal ulcer patients.

OBJECTIVE: It has been reported that the cytotoxin-associated gene A (cagA+) H. pylori strains induce severe gastric mucosal inflammation. The aim of this study was to investigate the association of the virulence factor CagA with IL-17 and IL-23 serum levels in duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers. METHODS: In total, 45 H. pylori-infected DU patients were enrolled to study: 23 tested positive for the anti-CagA antibody (anti-CagA+) and 22 tested negative for the anti-CagA antibody (anti-CagA-), 30 were AS carriers (15 were anti-CagA+ and 15 were anti-CagA-) and 15 were healthy uninfected participants (as a control group). The IL-17 and IL-23 serum levels of participants were measured by enzyme-linked immunosorbent assay method. RESULTS: The mean IL-17 levels in DU patients were significantly higher than those in AS and control groups (P < 0.001 and P < 0.0001 respectively). In the DU group, the mean IL-17 levels in participants testing positive for anti-CagA (10.84 +/- 5.79 pg/mL) were significantly higher than those observed in participants testing negative for anti-CagA (7.65 +/- 4.74 pg/mL; P < 0.05). The mean IL-23 levels in the DU and AS groups were significantly higher than in the control group (P < 0.02 and P < 0.03 respectively) but were not significantly different in participants testing positive and negative for anti-CagA. CONCLUSION: These results showed higher IL-17 and IL-23 serum levels in H. pylori-infected participants than in the control group. In the DU group the expression of IL-17 was influenced by the CagA factor.

Serum levels of interleukin (IL)-13, IL-17 and IL-18 in patients with ischemic heart disease.

OBJECTIVE: It has been reported that the cytokines play an important role in the pathogenesis of cardiovascular diseases. The aim of this study was to evaluate the serum levels of interleukin (IL)-13, IL-17 and IL-18 in patients with ischemic heart disease (IHD) and also to clarify their association with traditional risk factors of disease. METHODS: A total of 60 patients with IHD as having acute myocardial infarction (AMI; n=30) or unstable angina (UA; n=30) and 30 sex- and age- matched healthy subjects as a control group were enrolled to this cross-sectional, case-controlled study. Serum samples were collected from all participants (for AMI patients at 3-5 days after events and for UA at admission time) and tested for the IL-13, IL-17 and IL-18 by use of ELISA method. Statistical analysis was performed using ANOVA, Student t, Kruskal-Wallis, Mann-Whitney U and Chi-square tests as appropriate. RESULTS: The frequencies of subjects with detectable levels of IL-13 were 6.7%, 20% and 33.3% in AMI, UA and control groups, respectively. The frequency of subjects with detectable levels of IL-13 in control group was significantly higher as compared to AMI group and total group of patients with IHD (p<0.02 and p<0.05, respectively). The mean serum levels of IL-17 in AMI group (6.68+/- 1.2 pg/ml) and UA group (5.48+/- 1.01 pg/ml) were significantly higher than that observed in control group (2.07+/- 0.60 pg/ml; p<0.005 and p<0.04, respectively). Moreover, the mean serum levels of IL-18 in UA group (122.92+/- 18.16 pg/ml) were significantly higher than in control group (67.82+/- 5.98 pg/ml; p<0.03). The mean serum levels of IL-18 in IHD patients without a certain traditional risk factor including non-hypertensive patients (120.14+/- 17.04 pg/ml), non-dyslipidemic patients (131.86+/- 20.04 pg/ml), non-diabetic patients (111.96+/- 14.71 pg/ml) and non-smoker patients (113.93+/- 16.41 pg/ml) were significantly higher as compared to control group (p<0.04, p<0.004, p<0.03 and p<0.03, respectively). Although, the mean serum levels of IL-18 in patients with a certain traditional risk factor were higher in comparison to control group, but the differences were not significant. The means serum levels of IL-17 in patients with or without a certain traditional risk factor were also markedly higher as compared to healthy group. CONCLUSIONS: These results showed that the higher serum levels of IL-17 and IL-18 were associated with IHD. The presence or absence of a certain traditional risk factors of IHD may influence the serum levels of cytokines. These findings may be considered to improve the predictive or prognostic values of inflammatory cytokines for IHD and also to design possible novel therapeutic approaches.

Cigarette smoke-exposed saliva suppresses cellular and humoral immune responses in an animal model.

OBJECTIVE: To evaluate the effects of cigarette smoke (CS)-exposed saliva on cellular and antibody responses in an animal model. METHODS: The stimulatory and non-stimulatory saliva samples were collected from 10 healthy subjects and were then exposed to CS for 20 or 80 minutes. The CS-exposed saliva samples were administrated intraperitoneally (i.p) to male Balb/c mice. Then the delayed type hypersensitivity (DTH) and antibody responses to sheep red blood cell (SRBC) was assessed. Moreover, the total white blood cells (WBC) counts and the blood lymphocytes counts were determined. RESULTS: The mean of DTH responses of animal groups received 20 minutes or 80 minutes CS-exposed saliva samples was significantly lower than that observed in control group. Moreover, The mean titer of anti-SRBC antibody was significantly lower in animal groups who received 80 minutes CS-exposed stimulatory or non-stimulatory saliva as compared to control group (P < 0.04 and P < 0.002, respectively). The mean counts of blood lymphocytes in 80 minutes CS exposed-stimulatory saliva group was also significantly lower as compared to control group (P < 0.05). CONCLUSION: These results show that the CS-exposed saliva samples have profound suppressive effects on both cellular and humoral immune response in a mouse animal model.