Evaluation of alum-naltrexone adjuvant activity, on efficacy of anti-leishmania immunization with autoclaved leishmania major [MRHO/IR/75/ER] antigens in BALB/C mice

Naltrexone, an opioid receptor antagonist shifts the immune response toward a Th1 profile. In the current study, we evaluated the efficacy of the mixture of NTX and alum, as a new adjuvant, to enhance immune response and induce protection against Leishmania major in a mouse model. BALB/c mice were immunized three times either autoclaved L. major promastigotes' antigens alone or in combination with the adjuvant alum, naltrexone or the alum-naltrexone mixture. Both humoral and cellular immune responses were assessed two weeks after the last immunization and compared with control mice. The administration of alum- NTX in combination with the parasite antigen, significantly increased production of IFN- gamma, IFN-gamma /IL-5 ratio, lymphocyte proliferation and improved DTH response against L. major. There was no significant difference in survival following challenge among groups. Immunization with the alum- naltrexone mixture as an adjuvant, in combination with the autoclaved L. major promastigotes antigens, can enhance cellular immunity and shift the immune responses to a Th1 pattern

Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice

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, beta-AR blocker, against various cancers. To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. 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+ CD25[high] T-reg cells and IFN-gamma and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. A significant increase in the level of IFN- gamma 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-gamma. 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. HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses

effects of isoproterenol and propranolol on cytokine profile secretion by cultured tumor-infiltrating lymphocytes derived from colorectal cancer patients

Anti-tumor immunity and cytokine profiles have important roles in the development of cancer. Norepinephrine [NE] release due to sympathetic activation leads to a Th2 deviation via the beta-2 adrenergic receptor [beta -2AR] and could increase cancer progression. This study intends to determine the effects of isoproterenol [ISO; betaagonist] and propranolol [PRO; beta-antagonist] on the production of IFN-gamma, IL-4, and IL-17. Cytokine levels have been examined in tumor-infiltrating lymphocytes [TILs] and peripheral blood mononuclear cells [PBMCs] of patients with colorectal cancer [CRC]. The beta-2AR expression on lymphocyte subsets was also assessed. In this experimental study, TILs were isolated from fresh CRC tissue and patient PBMCs were obtained just prior to surgery. The cells were cultured in medium for 72 hours. Concomitantly, cells were stimulated with 10 micro g/ ml phytohemagglutinin [PHA] alone or in the presence of either 1 micro mol/L of PRO or 1 micro mol/L ISO. The concentration of cytokines in the supernatants was measured by ELISA. Three-color flow cytometry was used to determine the expression of beta-2AR on the lymphocyte subsets. Statistical analyses were performed via paired or independent t-test. Levels of IFN-gamma, IL-4 and IL-17 were elevated after PHA-stimulation of PBMCs and TILs. However, the elevation of IFN-gamma and IL-17 production by TILs in response to PHA was significantly lower than PBMCs. In the presence of ISO, the IFN-gamma/IL-4 ratio reduced in all groups, but this reduction was very low in TILs. Interestingly, the effects of PRO on cytokine production were, at least partially, comparable to those of ISO. Depressed levels of beta-2AR expression were demonstrated on CD4+IFN-gamma+ and CD4+IL-17+ lymphocytes in patients' PBMCs and TILs. This study has demonstrated the effects of ISO and PRO on cytokine production by TILs and determined beta-2AR expression on these cells. ISO failed to induce a shift toward the expected Th2 cytokine profile in CRC patients' TILs, which might be due to the downregulation of beta-2AR expression on TILs. Additionally, in this study, PRO induced a shift to a Th2 profile in PBMCs

Purified aged garlic extract modulates allergic airway inflammation in Balb/c Mice

Garlic is known as a potent spice and a medicinal herb with broad therapeutic properties ranging from antibacterial to anticancer and anticoagulant. Our previous studies have shown some immunoregulatory effects for aged garlic extract, suggesting a key role for 14-kD glycoprotein of garlic in shifting the cytokine pattern to T helper-1. In present study, we investigated the effect of 1, 2, and 3 times intraperitoneal injections of aged garlic extract on an established allergic airway inflammation in murine model [BALB/c mice]. The garlic extract, isolated by biochemical method, includes proteins precipitation by ammonium sulfate. After injection of the aged garlic extract, IFN-gamma, anti allergen specific IgE and IgG1 were measured in lavage and serum by ELISA and histological assessment was performed on the lung tissues. The results indicated that three-time intra peritoneal injections of the aged garlic extract caused a significant decrease in the hallmark criteria of allergic airway inflammation levels which included eosinophil percentage in lavage, peribronchial lung eosinophils, IgG1 level in lavage and serum, mucous producing goblet cells grade and peribronchial and perivascular inflammation. Our findings in the present research suggested that aged garlic extract has the potential of attenuation of inflammatory features of allergic airway inflammation in murine model

[Evaluation of cell proliferation and interleukine-4 and interferon gamma level measurement in Balb/c with experimental fibrosarcoma tumor by combination of Gp96-tumor peptide and naloxan]

In spite of the increasing progress in tumor treatment by current methods like surgery, chemotherapy and etc, medical sciences are unable to treat tumors. In this respect, immunology has opened a new window for tumor treatment; nowadays tumor immunotherapy is an accepted strategy for treatment of some tumors at least in some animal models. The goal of this study is the evaluation of immunotherapy using gp96- tumor peptide complex and its combination with naloxon as an opioid receptor antagonist to achieve of cellular immunity against tumors. In this study firstly, gp96 - tumor peptide complexes were purified from WEHI164 cells line using srivastava method. In the next stage, the mice, made tumoric before by the injection of tumor cells, then were divided in to four groups. Control group were injected by PBS, test group1 were injected by naloxon, test group2 were injected by gp96 - tumor peptide complex and test group3 were injected by combination of naloxon and gp96 - tumor peptide complex. To evaluation the efficacy of vaccination, after several days, tumor volume was recorded; then the mice were killed and the spleanic cells were extracted in sterile condition. MTT test was done for cells proliferation study. Supernatant of cultured cells were collected and assayed by ELISA kits for measuring IL-4 and IFN- gamma. Result of protein purification had showen, purified gp96 Isoform has Molecular Weight of 66 kilo dalton.Results of tumor volume had shown that, there is no significant difference between test and control groups. Results of MTT test had shown that, there is no significant difference between test and control groups. IL-4 assay study had showed that, there is no significant difference between test group1, group2 and control group but test group3 has significantly decreased in IL-4 amount when compared with control group. Results of IFN-gamma assay showed that, there is no significant difference between test group1 and control group, but test group2 and group3 has significantly increased in IFN- gamma amount when compared with control group. It can be concluded from this study is that, prophylactic immunotherapy of tumor by combination of gp96-tumor peptide complex and naloxon, can increase IFN- gamma, and, probably in a higher dosage, it may stimulate immune system more to become more potent to even decrease tumor volume

[ cross-sectional study of Latex allergy among operation room staff of hospitals of Tehran university of medical sciences, 1380-1381]

Latex allergy is a major occupational disease with prevalence nearly 5-17% among the health care workers. To determine the prevalence of latex glove allergy and its contributing factors among operation room staff. In this study, 512 operation room staff were evaluated for latex allergy, using a complete questionnaire. Those suspected to have latex allergy underwent these tests: Eosinophils counting, measurement of serum total and latex specific IgE, latex skin prick test, latex and glove additives patch test. From evaluated staff, 178 [34.8%] had a history of sensitivity to latex gloves, from which 59 persons underwent the tests voluntarily. According to the results of the tests, 13 [22%] had type I allergy to latex, 3 [5.1%] had type IV allergy to latex and 9 [15.3%] had both allergies. There were no significant relationship between latex allergy and age, sex, job, season, family and personal history of allergies. Significant relationship was found between type I allergy to latex and allergy to kitchen gloves and also between type IV allergy and allergy to other plastic clothing. Prevalence of latex allergy in this study is much higher than similar studies, which demands more evaluation to determine the contributing factors