Ahmad Khalili; Zuhair Muhammad Hassan; Shahram Shahabi; Ali Akbar Pourfathollah; Seyed Nasser Ostad; Shokoofe Noori; Mehdi Mahdavi; Habib Haybar; Ladan Langroudi
Volume 10, Issue 2 , June 2013, , Pages 70-82
Abstract
Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, ...
Read More
Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, antiangiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. Objectives: To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Methods: Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxic activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. Results: A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. Conclusion: HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.
Shokoofe Noori; Zuhair Mohammad Hassan; Omid Salehian
Volume 10, Issue 1 , March 2013, , Pages 10-21
Abstract
Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on ...
Read More
Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects on reducing the tumor volume and shifting the cytokine profile were investigated. We also assessed if intraperitoneally injected Sclareol could improve the outcome of cancer therapy through suppressing the regulatory T cells. Results: The results confirmed a significant decrease in the tumor size. Furthermore, a significant decrease in the level of IL-4 and an increase in the level of IFN-γ were noticed in the intraperitoneally injected Sclareol group (p<0.05). It was also observed that the splenocytes of treated animals significantly increase in cell proliferation assay. Moreover, measurements of splenic T regulatory cell indicated that intraperitoneally injected Sclareol significantly decreased the number of splenic T regulatory cell. Conclusion: Our results suggest that Sclareol, by reducing T-reg cells frequency and also tumor size can enhance the effect of cancer therapy as an immunostimulant.
Soghra Khazardoust; Pouya Javadian; Bahram Salmanian; Farnaz Zandevakil; Fatemeh Abbasalizadeh; Shohreh Alimohamadi; Sedigheh Borna; Tooba Ghazanfari; Sedigheh Hantoushzadeh
Volume 9, Issue 3 , September 2012, , Pages 199-207
Abstract
Background: There are strong evidences suggesting the secretion of different cytokines in cervical fluid during preterm labor. Betamethasone is widely administered for several reasons in preterm conditions. Objective: To Investigate the possible effect of betamethasone on endocervical cytokine concentration ...
Read More
Background: There are strong evidences suggesting the secretion of different cytokines in cervical fluid during preterm labor. Betamethasone is widely administered for several reasons in preterm conditions. Objective: To Investigate the possible effect of betamethasone on endocervical cytokine concentration of women at risk of preterm labor. Methods: In a randomized clinical trial of 80 prime-gravid women in preterm labor between 34 and 37 weeks of gestation, cervical fluid was collected. Endocervical concentration of inflammatory cytokines were analyzed before and 48 hours after betamethasone treatment for the evaluation of IL-8, IL-17, IFN-γ and TGF-β. Wilcoxon and Mann-Whitney tests were employed for statistical analysis. χ2 and Student’s t tests were used whenever needed. Results: All the measured cytokines showed significant changes in the betamethasone treated group. IL-17 (p=0.001), IL-8 (p=0.001), and IFN- γ (p<0.05) decreased significantly, while TGF-β had a significant increase (p<0.05). In the patients who delivered before or on the 7th day of admission, IL-17, IL-8, and IFN-γ levels were all significantly higher. However, TGF-β decreased significantly in the same samples in the betamethasone treated group (p<0.05). Conclusion: Betamethasone significantly decreases the endocervical pro-inflammatory cytokine concentrations in patients with preterm labor.
Mohammad Ali Ghayumi; Zahra Mojtahedi; Mohammad Javad Fattahi
Volume 8, Issue 4 , December 2011, , Pages 195-200
Abstract
Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) ...
Read More
Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) (Th1 cytokines) in malignant and non-malignant pleural effusions. Method: The cytokine levels in pleural fluid of 62 patients with malignant pleural effusion (44 with lung cancer and 18 with extrathoracic tumors), 8 with tuberculous and 8 with congestive heart failure pleural effusion were analysed using enzymelinked immunosorbent assays. Results: IL-2 was below the detectable concentration of the assay. A significant decrease in IFN-γ level was observed in malignant but not in congestive heart failure cases compared to tuberculous cases. IL-10 levels were higher in malignant and tuberculous pleural effusions than in congestive heart failure pleural effusions, however, this difference did not reach the significant level. IL-4 levels were also increased non-significantly in lung cancer pleural effusions compared to the other groups. Conclusion: Our results show a wide variation in IL-4, IL-10, and IFN-γ levels in malignant pleural effusions, a pattern which was not convincing enough to differentiate the cause of effusion.
Shahid Hussain; Nadeem Afzal; Khursheed Javaid; Muhammad Ikram Ullah; Tanveer Ahmad; Saleem-Uz -Zaman
Volume 7, Issue 4 , December 2010, , Pages 240-246
Abstract
Background: Interferon gamma (IFN-γ), a cytokine produced by a variety of cells is involved in the immune response against M. tuberculosis. It activates the production of other cytokines and molecules that kill mycobacterium. IFN-γ also has diagnostic role in identification of active and ...
Read More
Background: Interferon gamma (IFN-γ), a cytokine produced by a variety of cells is involved in the immune response against M. tuberculosis. It activates the production of other cytokines and molecules that kill mycobacterium. IFN-γ also has diagnostic role in identification of active and latent tuberculosis. Objective: To determine the level of IFN-γ in the blood of TB patients. Methods: Ninety-one subjects were selected, including 54 active TB patients and 37 healthy controls. Among 54 TB patients, 27 had confirmed TB and 27 were clinically diagnosed as having TB. IFN-γ concentration was determined in their blood by an ELISA technique. Results: In TB patients, Mean + SD of IFN-γ was 48.69 + 28.78 pg/ml while it was 12.99 + 5.70pg/ml in the control group (p <0.001). Significant differences in the level of IFN-γ were observed among confirmed TB patients, clinically diagnosed TB patients and the control group (Mean + SD 59.68 + 28.78, 36.85 + 24.76 and 12.99 + 5.70 pg/ml, respectively). Furthermore, a significant negative correlation was observed between the concentration of IFN-γ in TB patients and the duration of antituberculosis therapy. Conclusion: IFN-γ level was high in both clinically diagnosed and confirmed TB patients as compared to a control group. Measurement of IFN-γ production is helpful to diagnose active tuberculosis, but further research is required.
Mehdi Mahdavi; Masoumeh Ebtekar; Fereidoun Mahboudi; Hamidreza Korram Khorshid; Fatemeh Rahbarizadeh; Kayhan Azadmanesh; Haydeh Darabi; Farzaneh Pourasgari; Zuhair Mohammad Hassan
Volume 6, Issue 4 , December 2009, , Pages 163-173
Abstract
Background: Cell mediated immunity, especially cytotoxic T cell responses against HIV-1 infection, plays a critical role in controlling viral replication and disease progres-sion. DNA vaccine is a novel technology which is known to stimulate strong cellular immune responses. Many DNA vaccines have been ...
Read More
Background: Cell mediated immunity, especially cytotoxic T cell responses against HIV-1 infection, plays a critical role in controlling viral replication and disease progres-sion. DNA vaccine is a novel technology which is known to stimulate strong cellular immune responses. Many DNA vaccines have been tested for HIV infection but there is still no effective vaccine against this infection. Construction of a vaccine consisting of multiple conserved and immunogenic epitopes may increase vaccine efficacy. Objective: In the present study, a DNA vaccine candidate constructed from HIV-1 P24-Nef was evaluated and cellular immune responses were assessed in murine BALB/c model. Methods: HIV-1 P24-Nef gene was cloned in pCDNA3.1 expression vector. Mice were immunized with DNA construct and IL-4 and IFN-γ evaluation was per-formed using ELISPOT. Cytotoxicity response was evaluated with Granzyme B ELIS-POT assay and lymphocyte proliferation was evaluated with LTT assay. Results: Analysis of immune responses showed that, compared to control groups, the candidate vaccine induced production of higher levels of both IL-4 and IFN-γ (p<0.05). Cytotox-icity and lymphocyte proliferation responses of mice vaccinated with the candidate vac-cine were significantly increased compared to control groups (p<0.05). Conclusion: HIV-1 P24-Nef DNA construct displayed strong immunogenicity in a murine model.
Shokoofe Noori; Mohammad Taghikhani; Zuhair M. Hassan; Abdolamir Allameh; Ali Mostafaei
Volume 6, Issue 4 , December 2009, , Pages 216-224
Abstract
Background: Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group (Tehranolide). Objective: Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this ...
Read More
Background: Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group (Tehranolide). Objective: Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this study, the immunotherapeutic effec-tiveness of Tehranolide was investigated by direct intra-tumoral injection. Methods: Tehranolide was purified from Artemisia diffusa, and its effect on the tumor volume was investigated. The splenocyte proliferation, shifting of cytokine profile, and the presence of naturally-occurring CD4+CD25+Foxp3+ Treg cells were assessed to describe the anti-tumor immune response. Results: Analysis of immune response showed that, intra-tumoral injection of Tehranolide decreased the rate of tumor growth compared to control group. Furthermore, the proliferative response of mice treated with Tehranolide was en-hanced. In comparison with the control group, production of both IL-4 and IFN-γ was in-duced (p<0.05). The results indicated a decrease in tumor CD4+CD25+Foxp3+ T lym-phocytes in the Tehranolide-treated group compared to the control group. Conclusion: Treatment of tumors with Tehranolide attenuated CD4+CD25+Foxp3+ Treg cell-mediated immune suppression and elicited a persistent anti-tumor immunity against can-cer.
Kazem Ahmadi; Majid Riazipour
Volume 5, Issue 3 , September 2008, , Pages 177-180
Abstract
Background: T-2 toxin is a mycotoxin of type A trichothecenes produced by several fungal genera such as Fusarium species. Mycotoxins can affect both cell mediated and humoral immune compartments. Objective: The purpose of this study was to investi-gate the effect of T-2 toxin on cytokine production by ...
Read More
Background: T-2 toxin is a mycotoxin of type A trichothecenes produced by several fungal genera such as Fusarium species. Mycotoxins can affect both cell mediated and humoral immune compartments. Objective: The purpose of this study was to investi-gate the effect of T-2 toxin on cytokine production by mouse peritoneal macrophages and lymph node T cells. Methods: Mouse peritoneal macrophages and lymph node T cells were isolated and treated with different concentrations of T-2 toxin and incubated at 370C and 5% CO2 in air for 48 hours. Cell free media were removed and used for cy-tokine assay by an ELISA method. Results: T-2 toxin significantly reduced IL-1β re-lease in a concentration dependent manner (p<0.005, p<0.001). Interleukin-12 and TNF-α production were significantly increased in response to 0.001ng/ml, 0.01ng/ml and 0.1ng/ml of T-2 toxin (p<0.001). However, T-2 toxin at higher concentrations rang-ing from 1ng/ml to 100ng/ml, reduced both IL-12 (p<0.001) and TNF-α production (p<0.005, p<0.05). The effects of T-2 toxin on lymph node T cells showed that IL-4 and IL-10 release was decreased in a concentration dependent manner (all with p<0.01). T-2 toxin at concentrations between 1ng/ml and 100ng/ml reduced the release of both IL-2 and IFN-γ (p<0.05, p<0.001). Conclusion: The results suggest that T-2 toxin at low concentrations can highly induce secretion of IL-12, TNF-α, IFN-γ and IL-2 and it may be used as a positive immunomodulator in the human model.
Elmuataz Elmansi Abdalla
Abstract
Background: Gastrointestinal hormones have traditionally been viewed as mere regulators of gut movement and secretions, but, it is becoming increasingly apparent that other body systems may be affected by these hormones. Secretion of gut hormones is influenced by the type of food we take. Therefore, ...
Read More
Background: Gastrointestinal hormones have traditionally been viewed as mere regulators of gut movement and secretions, but, it is becoming increasingly apparent that other body systems may be affected by these hormones. Secretion of gut hormones is influenced by the type of food we take. Therefore, the more we know about the effects of gut hormones on the various body tissues, the more we know about the different mechanisms by which our diets affect our health. Objectives: This in vitro study aimed to explore the effects of physiologically-relevant concentrations of four gut hormones on the production of IL-2 and IFN- gamma by human peripheral blood mononuclear cells and how culture conditions may modify those effects. Methods: Peripheral blood mononuclear cells were separated by density gradient centrifugation from the blood of 15 adults. Cells were cultured with/without PHA and treated with four concentrations of gastrin, secretin, GIP and VIP. IL-2 and IFN- gamma in culture supernatants were assayed by ELISA. Results: Gastrin, secretin, GIP and VIP increased IL-2 and IFN- gamma levels under some culture conditions and depressed IL-2 under other conditions. An increase was often observed under culture conditions in which the cytokine production was not initially high. Repeated administration of the hormone was also more likely to result in a stimulatory effect. Conclusions: Physiologically-relevant concentrations of gastrin, secretin, GIP and VIP are potential immunomodulators as they have shown their ability to alter the production of IL-2 and/or IFN- gamma under various culture conditions.
