Acute noise-induced alterations in the immune status of albino rats

The effect of acute noise induced changes on the immune functions of albino rats was studied. Cell mediated immunity was assessed by Leukocyte migration inhibition index (LMI) and humoral immunity by estimating antibody titre. The organ weight of spleen, thymus, adrenal and lymph node was noted, the cell count of spleen and thymus was enumerated and plasma corticosterone level was estimated. A significant increase in the plasma corticosterone level, thymus weight and cell count along with significant decrease in the antibody titre, spleen weight and cell count was observed in noise stressed animals. No significant changes were observed in the LMI and organ weight of adrenal and lymph node in these animals. Our study shows acute noise to be a potent stressor causing definite alterations in the immune functions of the albino rats.     

Role of corticosteroids in cadmium induced immunotoxicity

Cadmium chloride at doses of 30, 100 and 300 ppm was orally fed to swiss albino mice for 35 days and the humoral and cell mediated immunity was studied by measuring the haemagglutination titre and delayed type hypersensitivity response respectively. Further, the blood corticosteroid level was determined in all the groups. Cadmium at doses of 100 and 300 ppm was found to significantly (p < 0.05) suppress both humoral and cellular immunity with simultaneous increase in the level of blood corticosterone and aldosterone. In order to assess whether the suppression of immune response in cadmium exposed mice is mediated by corticosteroids, aminoglutethemide, an adrenal blocker was administered to mice along with cadmium and the immune response was studied. Aminoglutethemide when administered alone caused significant (p < 0.05) stimulation of immunoglobulin level and delayed type hypersensitivity response as compared to cadmium (300 ppm) fed mice. When co-administered with cadmium, the cadmium induced immunosuppression was reversed back to normal. The results of this study indicate the involvement of adrenal hormones in cadmium induced immunosuppression suggesting that cadmium activates the corticosteroid associated immunoregulatory circuit.     

Possible role of histamine receptors in the central regulation of immune responses

The present study was designed to delineate the role of H1- and H2-histamine receptors in the neuro-immune regulation in rats. The effects of H1- and H2-receptor antagonists on humoral and cell-mediated immune (HI and CMI) responses were investigated after intraperitoneal (i.p.) and intra-cerebroventricular (i.c.v.) administration. HI response was assayed by anti-sheep red blood cell (SRBC) antibody titre in presence and absence of 2-mercaptoethanol (2-ME). The CMI responses were evaluated by delayed type hypersensitivity (DTH) reaction (in vivo), i.e., measurement of footpad thickness, and lymphokine activity such as leucocyte migration inhibition (LMI) test (in vitro). On i.p. administration, both H1- (pheniramine and astemizole) and H2-receptor antagonists (ranitidine and cimetidine) were observed to produce significant enhancement of anti-SRBC antibody response. However, only H2- and not H1-receptor blockers were observed to stimulate CMI response significantly. When administered by icv route, only H2-receptor antagonists caused a statistically significant increase in both HI and CMI responses, while the H1-receptor blockers failed to modify the same. Thus, H2-receptors appear to play a major role in the histaminergic mechanisms involved in immunomodulation both at the level of immunocompetent cells active in the peripheral tissues as well as through the central nervous system structures involved in the central regulation of neuro-immune interaction.     

Immune Response to Nasal Delivery of Antigenically Intact Tetanus Toxoid Associated with Poly(l-lactic acid) Microspheres in Rats,Rabbits and Guinea-pigs

Abstract— Tetanus toxoid was adsorbed onto poly(l -lactic acid) microspheres. Analyses by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting suggest that the formulation procedure does not affect the stability or the antigenic properties of the protein. After nasal administration to guinea-pigs, the resulting preparation enhanced the immune response to the tetanus toxoid when compared with the free antigen. The increase in systemic immunoglobulin G titre was almost immediate in the group treated with the adsorbed tetanus toxoid (time zero, 140; week 2, 1550; week 4, 2760), reaching 36000 two weeks after the booster (week 7), whereas the free antigen produced an immune response similar to that found in non-treated animals. In a parallel experiment, latex particles of a similar size to poly(l -lactic acid) microspheres, administered to both rats and rabbits, were detected in the blood stream. These findings with tetanus toxoid demonstrate the use of microsphere delivery systems for nasal application of antigens. These had a profound effect on the immune response, and indicate possibilities for overcoming some of the barriers to drug absorption in general.     

Role of Corticosteroids In Cadmium Induced Immunotoxicity

ABSTRACT

Cadmium chloride at doses of 30, 100 and 300 ppm was orally fed to swiss albino mice for 35 days and the humoral and cell mediated immunity was studied by measuring the haemagglutination titre and delayed type hypersensitivity response respectively. Further, the blood corticosteroid level was determined in all the groups. Cadmium at doses of 100 and 300 ppm was found to significantly (p<0.05) suppress both humoral and cellular immunity with simultaneous increase in the level of blood corticosterone and aldosterone. In order to assess whether the suppression of immune response in cadmium exposed mice is mediated by corticosteroids, aminoglutethemide, an adrenal blocker was administered to mice along with cadmium and the immune response was studied. Amino glutethemide when administered alone caused significant (p<0.05) stimulation of immunoglobulin level and delayed type hypersensitivity response as compared to cadmium (300 ppm) fed mice. When co-administered with cadmium, the cadmium induced immunosuppression was reversed back to normal. The results of this study indicate the involvement of adrenal hormones in cadmium induced immunosuppression suggesting that cadmium activates the corticosteroid associated immunoregulatory circuit.     

Immunosuppressive activity of a polychlorinated diphenyl preparation on the humoral immune response in guinea pigs

Three groups of 12 female albino guinea pigs were fed 0, 10 and 50 ppm Aroclor 1260 (PCB) for 8 wk. In half of the animals a function test of the immunological system was carried out: tetanus toxoid injection was used to study the humoral response. At the end of the experiment cellulose acetate electrophoresis was used to determine the serum proteins, including the γ-globulin level. The number of γ-globulin-containing cells in popliteal lymph nodes was determined semiquantitatively with the direct fluorescent antibody technique. Both these techniques seemed to be sensitive parameters for the immunosuppressive action of PCB in the tetanus toxoid-stimulated animals.     

Effects of combinations of endosulfan, dimethoate and carbaryl on immune and hematological parameters of rats.

IgG and IgM levels and hematological parameters (red and white blood cell counts, thrombocyte, monocyte, lymphocyte and granulocyte counts and hemoglobin concentrations) were determined in albino rats exposed to combinations of endosulfan, dimethoate and carbaryl. Two and 3 combinations of 100- and 1000-fold acceptable daily intake (ADI) of endosulfan (ADI = 0.00612 mg/kg), dimethoate (ADI = 0.0204 mg/kg) and carbaryl (ADI = 0.0101 mg/kg) were administered po to male albino rats for 3.5 mo. Animals were immunized s.c. with tetanus toxoid in Freund's complete adjuvant 20 d before terminating exposures. At 100-fold ADI dosing, administration of each of the pesticides alone did not cause any difference in the parameters, but numbers of white blood cells and monocytes increased in rats given endosulfan + dimethoate while numbers of red blood cells increased with dimethoate + carbaryl. Rats given 1000-fold ADI endosulfan + dimethoate + carbaryl had significant differences in almost every parameter, while IgG, IgM white blood cells and lymphocytes decreased, and monocytes and % granulocytes increased from single endosulfan dosing. Lymphocyte counts were reduced by single dimethoate or carbaryl dosing. Endosulfan + dimethoate + carbaryl produced the most effective changes in comparison to single dosing or other pesticide combinations.     

Effect of L-arginine on restraint stress induced modulation of immune responses in rats and mice.

The present study investigates the role of nitric oxide (NO) on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses in rats and mice. RS produced suppression of humoral immune response, i.e., anti-SRBC antibody titre ( 7.38 +/- 0.32 versus 4.13 +/- 0.30; mean +/- S.E.M., P < 0.001). In case of cell-mediated immunity, in delayed type hypersensitivity (DTH) response the change in paw volume decreased from 0.069 +/- 0.003 mm (mean +/- S.E.M.) in control non-stressed group to 0.038 +/- 0.002 mm in the stressed group (P < 0.001) while percentage leucocyte migration inhibition (% LMI) decreased from 39.7 +/- 1.95 in control non-stressed animals to 15.2 +/- 1.07 in animals subjected to stress (P < 0.01). Pretreating the animals with an NO precursor, L-arginine (1000 mg kg-1, i.p.) antagonized the effect of RS on humoral (anti-SRBC antibody titre 6.50 +/- 0.27 versus 4.13 +/- 0.30, P < 0.001 ) and cell-mediated (DTH response 0.066 +/- 0.002 mm versus 0.038 +/- 0.002 mm, P < 0.001; % LMI 41.5 +/- 1.46 versus 15.2 +/- 1.07, P < 0.01) immune responses. Administration of 7-nitroindazole (7-NI, 50 mg kg-1, i.p.), an inhibitor of neuronal NO synthase, alone further enhanced the immunosuppressive effect of RS (anti-SRBC antibody titre 2.75 +/- 0.25 versus 4.13 +/- 0.30, P < 0.001; DTH response 0.019 +/- 0.002 mm versus 0.038 +/- 0.002 mm, P < 0.001; % LMI 5.0 +/- 1.08 versus 15.2 +/- 1.07, P < 0.01). However, when given before L-arginine treatment, 7-NI reversed the effect of the latter drug on stress-induced immunomodulation (anti-SRBC antibody titre 3.00 +/- 0.27 versus 6.5 +/- 0.27, P < 0.001; DTH response 0.043 +/- 0.003 mm versus 0.066 +/- 0.002 mm, P < 0.001; % LMI 12.0 +/- 0.93 versus 41.5 +/- 1.46, P < 0.01). Unlike its effect on RS-induced immune responsiveness, L-arginine (250, 500, 1000 mg kg-1) when given for 5-7 days to naive non-stressed animals produced dose dependent suppression of both humoral (anti-SRBC antibody titre 6.4 +/- 0.32 versus 5.4 +/- 0.32, 4.0 +/- 0.27, 3.1 +/- 0.30, respectively) and cell-mediated (DTH 0.065 +/- 0.003 mm versus 0.064 +/- 0.004 mm, 0.039 +/- 0.003 mm, 0.020 +/- 0.002 mm, respectively and % LMI 37.52 +/- 1.58 versus 30.48 +/- 1.07, 28.18 +/- 1.22, 19.76 +/- 0.83, respectively) immune responses. 7-NI significantly blocked these immunosuppressive effects of L-arginine (anti-SRBC antibody titre 6.0 +/- 0.38 versus 3.1 +/- 0.030, P < 0.01; DTH response 0.056 +/- 0.004 mm versus 0.020 +/- 0.002 mm, P < 0.001; % LMI 34.76 +/- 1.31 versus 19.76 +/- 0.83, P < 0.01). However, 7-NI when given to non-stressed animals failed to modulate immune responsiveness. Thus, NO appears to play an important role in RS-induced immunomodulation and these effects are different from its effect on immune responsiveness in non-stressed animals.     

Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice.

Immunosuppression of humoral and cellular responses following chronic oral exposure to 1, 5, 10, and 20 ppm N-nitrosodimethylamine (NDMA) was examined in CD-1 mice. Monitoring of cumulative mortality and the incidence of peritoneal ascites in animals showed an NDMA dose-related mortality and hepatotoxicity. No visible changes in immunological parameters were noted at the 1 ppm NDMA dose. Immunosuppression of immunoglobulin M (IgM) antibody response by NDMA to sheep red blood cells (SRBC) was time-related, dose-related, and could be reversed within 30 d by removal of the chemical from the drinking water. Cellular immune response, monitored by allogeneic stimulation of cells in mixed lymphocyte reaction (MLR), was markedly suppressed by 10 and 20 ppm NDMA. Thus, chronic exposure to NDMA, except for the low-hepatotoxic doses of nitrosamine, resulted in a marked and persistent immunosuppression of cellular and humoral responses in CD-1 mice. In conclusion, chronic exposure to the hepatotoxic (ascite-inducing) doses of NDMA suppressed humoral and cellular immunity. The persistent immunosuppression could be reversed after the removal of NDMA from the drinking water. Although no direct NDMA-related cancer was reported in humans, our data point to a potential epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression.     

Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced immune responses by bicuculline

The present study investigates the effect of progesterone, a pregnane precursor of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for mitochondrial diazepam binding inhibitor receptor (MDR) involved in neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses. RS produced a significant reduction in anti-sheep red blood cells (SRBC) antibody titre, a measure of humoral immune response, and % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of cell-mediated immune responses. These effects of RS on immune responses were effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc) or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS. The effect of both progesterone and 4'-CD on RS-induced immune modulation was significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10 mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone (5, 10 mg/kg, sc) when administered to non-stressed animals produced a significant suppression of both humoral and cell-mediated immune responses which was not reversed by bicuculline. However, 4'-CD failed to modulate immune response in naive non-stressed animals. These results suggest that progesterone and 4'-CD affect stress-induced immune responses by modulating GABA-ergic mechanism. However, GABA-A receptor system does not appear to be involved in progesterone-induced immunosuppression in nonstressed animals.     

Tetanus toxoid-loaded transfersomes for topical immunization

Topical immunization is a novel immunization strategy by which antigens and adjuvants are applied topically to intact skin to induce potent antibody and cell-mediated responses. Among various approaches for topical immunization, the vesicular approach is gaining wide attention. Proteineous antigen alone or in combination with conventional bioactive carriers could not penetrate through the intact skin. Hence, specially designed, deformable lipid vesicles called transfersomes were used in this study for the non-invasive delivery of tetanus toxoid (TT). Transfersomes were prepared and characterized for shape, size, entrapment efficiency and deformability index. Fluorescence microscopy was used to investigate the mechanism of vesicle penetration through the skin. The immune stimulating activity of these vesicles was studied by measuring the serum anti-tetanus toxoid IgG titre following topical immunization. The immune response was compared with the same dose of alum adsorbed tetanus toxoid (AATT) given intramuscularly, topically administered plain tetanus toxoid solution, and a physical mixture of tetanus toxoid and transfersomes again given topically. The results indicated that the optimal transfersomal formulation had a soya phosphatidylcholine and sodium deoxycholate ratio of 85:15%, w/w. This formulation showed maximum entrapment efficiency (87.34 +/- 3.81%) and deformability index (121.5 +/- 4.21). An in-vivo study revealed that topically administered tetanus toxoid-loaded transfersomes, after secondary immunization, elicited an immune response (anti-TT-IgG) comparable with that produced by intramuscular AATT. Fluorescence microscopy revealed the penetration of transfersomes through the skin to deliver the antigen to the immunocompetent Langerhans cells.     

Humoral and cell mediated immune response to cadmium in mice

The effect of 30, 100 and 300 ppm of cadmium chloride (CdCl2) exposure for 35 days on humoral and cell mediated immune response was examined in Swiss Albino mice. Body burden of cadmium in kidney, spleen and liver was determined and histopathology of these organs was also done. Cadmium chloride in doses of 100 and 300 ppm when fed in drinking water caused significant decrease in IgM and IgG titre against sheep red blood cells (SRBC) and a significant decrease in IgG titre against bovine serum albumin (BSA). The delayed type hypersensitivity response to SRBC and splenic T cell proliferation to BSA was also significantly decreased following 100 amd 300 ppm cadmium exposure. Cadmium accumulation in the spleen, liver and kidney was associated with degeneration and inflammatory changes. It is concluded that cadmium causes significant suppression of humoral and cell mediated immune response in mice which could be due to its cytotoxic action on liver, kidney and immune cells.     

HUMORAL AND CELL MEDIATED IMMUNE RESPONSE TO CADMIUM IN MICE

The effect of 30, 100 and 300 ppm of cadmium chloride (CdCl₂) exposure for 35 days on humoral and cell mediated immune response was examined in Swiss Albino mice. Body burden of cadmium in kidney, spleen and liver was determined and histopathology of these organs was also done. Cadmium chloride in doses of 100 and 300 ppm when fed in drinking water caused significant decrease in IgM and IgG titre against sheep red blood cells (SRBC) and a significant decrease in IgG titre against bovine serum albumin (BSA). The delayed type hypersensitivity response to SRBC and splenic T cell proliferation to BSA was also significantly decreased following 100 amd 300 ppm cadmium exposure. Cadmium accumulation in the spleen, liver and kidney was associated with degeneration and inflammatory changes. It is concluded that cadmium causes significant suppression of humoral and cell mediated immune response in mice which could be due to its cytotoxic action on liver, kidney and immune cells.     

Does high organochlorine (OC) exposure impair the resistance to infection in polar bears (Ursus maritimus)? Part I: Effect of OCs on the humoral immunity

This study was undertaken to assess if high levels of organochlorines (OCs) are associated with decreased ability to produce antibodies in free-ranging polar bears (Ursus maritimus) and thus affect the humoral immunity. In 1998 and 1999, 26 and 30 polar bears from Svalbard, Norway, and Churchill, Canada, respectively, were recaptured 32-40 d following immunization with inactivated influenza virus, reovirus, and herpes virus and tetanus toxoid. Blood was sampled at immunization and at recapture for determination of plasma levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), serum immunoglobulin G (IgG) concentrations, and specific antibodies against influenza virus, reovirus, and herpes virus, tetanus toxoid, and Mannheimia haemolytica. The OCs alone contributed with up to 7% to the variations in the immunological parameters. The combination of sigma PCBs (sum of 12 individual PCB congeners), sigma OCPs (sum of 6 OCPs), and biological factors accounted for 40-60% of the variation in the immunological parameters. Negative associations were found between sigma PCBs and serum immunoglobulin G (IgG) levels and between sigma PCBs and increased antibody titers against influenza virus and reovirus following immunization. In contrast, a positive association was registered between sigma PCBs and increased antibodies against tetanus toxoid. sigma OCPs also contributed significantly to the variations in the immunological responses. OCs did not have the same impact on the antibody production against M. haemolytica. The present study demonstrated that high OC levels may impair the polar bears ability to produce antibodies and thus may produce impaired resistance to infections.     

Ozone-induced modulation of cell-mediated immune responses in the lungs

Most pulmonary immunotoxicology studies of ambient pollutants have been broadly designed to discern if overall humoral or cell-mediated immunity (CMI) was altered; few have assessed effects on particular aspects of immune function. We hypothesized that effects from ozone (O3) exposure on pulmonary CMI are linked in part to changes in local immune cell capacities to form and/or to interact with immunoregulatory cytokines. Rats exposed to 0.1 or 0.3 ppm O3 4 h/day 5 days/week, for 1 or 3 weeks were assessed for resistance to, and pulmonary clearance of, a subsequent Listeria monocytogenes challenge. In situ cytokine release and immune cell profiles were also analyzed at different stages of the antilisterial response. Although O3 exposure modulated CMI, effects were not consistently concentration- or duration-dependent. Exposure did not effect cumulative mortality from infection, but induced concentration-related effects upon morbidity onset and persistence. All 1-week exposed rats had listeric burdens trending higher than controls; 0.3 ppm rats displayed continual burden increases rather than any onset of resolution. Rats exposed for 3 weeks had no O3-related changes in clearance. No exposure-related effect on neutrophil or pulmonary macrophage (PAM) numbers or percentages was noted. Bacterial burden analyses with respect to cell type showed that Listeria:PAM ratios in 0.3 ppm rats ultimately became greatest compared to all other rats. In situ IL-1alpha and TNFalpha levels were consistently higher in O3-exposed rats. All rats displayed increasing in situ IFNgamma levels as infection progressed, but no constant relationship was evident between IFNgamma and initial IL-1alpha/TNFalpha levels in O3-exposed hosts. It seems that short-term (i.e., 1 week) repeated O3 exposures imparted more effects upon CMI than a more prolonged (i.e., 3 week) regimen, with effects manifesting at the level of the PAM and in the cytokine network responsible for immunoactivation.     

Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats

1-Bromopropane (1-BP) is categorized as a high-production-volume chemical and is currently used in the manufacture of pharmaceuticals, pesticides, and other chemicals. Its usage is estimated to be around 5 million pounds per year, resulting in the potential for widespread exposure in the workplace. Case reports and animal studies have suggested exposure to this compound may cause adverse reproductive and neurological effects. Using a battery of immunological assays, the immunotoxicity of 1-BP after whole body inhalation exposure in both mice and rats was evaluated. Significant decreases in the spleen immunoglobulin (Ig) M response to sheep red blood cells (SRBC) were observed in both mice (125–500?ppm) and rats (1000?ppm) after exposure to 1-BP for 10?wk. In addition, total spleen cells and T cells were significantly decreased after approximately 4?wk of 1-BP exposure in both mice (125–500?ppm) and rats (1000?ppm). No change in natural killer (NK) cell activity was observed. The observed alterations in spleen cellularity, phenotypic subsets, and impairment of humoral immune function across species raise further concern about human exposure to 1-BP and demonstrate the need for additional investigations into potential adverse health effects.     

Rat hippocampus and primary immune response

During immune challenge hippocampal region shows time-dependent changes in neurotransmitter levels. Hence in the present study the effect of electrolytic lesion in the dorsolateral hippocampus (DLH) and ventral hippocampal formation (VHF) (to create a disturbance in neurotransmitter levels) on humoral immunity in albino rats has been studied along with appropriate controls. Haemagglutination titre, IgM and IgG levels were monitored on the 5th day after an immune challenge by sheep red blood cells (SRBC) suspension. Antigen challenged lesioned animals had low circulating antibody titre levels compared with the controls and their site-specific sham lesioned groups. The IgM levels were significantly lowered in both DLH and VHF lesioned and immunized animals compared to their immunized sham groups as well as immunized controls. However, only immunized VHF lesioned group showed a significant decrease in IgG level from their immunized sham group. It was concluded from the results that an intact hippocampal region is essential for the normal humoral immunity for the primary immune response in rats. Probably VHF region may be required for the secondary immune response as indicated by the alteration in IgG levels in these animals.     

Effect of Hexachlorobenzene on the Immune System of Rats Following Combined Pre- and Postnatal Exposure

ABSTRACT

The effect of HCB on the immune system was studied after combined pre- and postnatal exposure. Pregnant rats received diets containing 50 and 150 mg HCB/kg. Dosing continued during lactation and after weaning. At an age of 5 weeks the immune system was functionally assessed. in both treatment groups, the resistance to L.mono-cytogenes infection was suppressed, as was the resistance to an infection with T. spiralis (increased yield of muscle larvae). No effect was observed on allograft rejection or on mitogenic response of thymus and spleen cells. HCB enhanced the thymus-dependent antibody response to T.spiralis antigen and to tetanus toxoid (secondary IgG titers to tetanus toxoid were increased 16-fold in both test groups). No effect was found on the thymus-independent IgM response to LPS, on the passive cutaneous anaphylaxis and on the clearance of carbon particles and L.monocytogenes. HCB treatment caused morphologic changes in lymph nodes, lung and liver. It is concluded that HCB suppresses cellular immunity and enhances humoral immunity in both test groups. As effects on liver (increase in weight and microscopic changes) were only noted in the 150 mg/kg group, it is also concluded that the developing immune system seems particularly vulnerable to HCB.     

Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration

The present study was designed with the objective to investigate the stability and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting immune response following oral administration. GM-bilosomes exhibited desired quality attributes simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations. The GM-bilosomes exhibited excellent stability in different simulated biological fluids and sustained release profile up to 24 h. GM-bilosomes elicited significantly higher (P < 0.05) systemic immune response (serum IgG level) as compared to bilosomes, niosomes and alum adsorbed TT administered through oral route. More importantly, GM-bilosomes were found capable of inducing mucosal immune response, i.e. sIgA titre in salivary and intestinal secretions as well as cell mediated immune response (IL-2 and IFN-γ levels in spleen homogenate) which was not induced by i.m. TT, the conventional route of immunization. Conclusively, GM-bilosomes could be considered as a promising carrier and adjuvant system for oral mucosal immunization.From the Clinical EditorThis team reports on the development and effects of a glucomannan-modified bilosome as an oral vaccine vector, using tetanus toxoid in the experiments. These GM-bilosomes not only elicited significantly higher systemic immune response as compared to bilosomes, niosomes and alum adsorbed orally administered TT, but also demonstrated mucosal immune response induction as well as cell mediated immune responses, which were not induced by the conventional route of immunization.     

Active immunization with angiotensin I peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin I in conscious rats

1. Male, Sprague-Dawley rats were actively immunized with novel angiotensin vaccines, and their pressor responses to exogenous angiotensin I (AI) and angiotensin II (AII) were assessed in vivo. Serum antibody titres were also measured. 2. The most effective vaccine consisted of an AI analogue conjugated with a tetanus toxoid carrier protein and adjuvanted with aluminium hydroxide. When this vaccine was injected on days 0, 21 and 42, pressor responses to AI on day 63 were significantly inhibited (maximum, 8.9 fold shift), but responses to AII were unaffected. The anti-angiotensin antibody titre was increased 32,100 fold, and, uniquely, these antibodies also cross-reacted with angiotensinogen. 3. These findings indicate that active immunization against AI may be a useful approach for treating cardiovascular disorders involving the renin-angiotensin system.