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PubMed2003

TGF-beta regulates airway responses via T cells.

Allergic asthma is characterized by airway hyperreactivity, inflammation, and a Th2-type cytokine profile favoring IgE production. Beneficial effects of TGF-beta and conflicting results regarding the role of Th1 cytokines have been reported from murine asthma models. In this study, we examined the T cell as a target cell of TGF-beta-mediated immune regulation in a mouse model of asthma. We demonstrate that impairment of TGF-beta signaling in T cells of transgenic mice expressing a dominant-negative TGF-beta type II receptor leads to a decrease in airway reactivity in a non-Ag-dependent model. Increased serum levels of IFN-gamma can be detected in these animals. In contrast, after injection of OVA adsorbed to alum and challenge with OVA aerosol, transgenic animals show an increased airway reactivity and inflammation compared with those of wild-type animals. IL-13 levels in bronchoalveolar lavage fluid and serum as well as the number of inducible NO synthase-expressing cells in lung infiltrates were increased in transgenic animals. These results demonstrate an important role for TGF-beta signaling in T cells in the regulation of airway responses and suggest that the beneficial effects observed for TGF-beta in airway hyperreactivity and inflammation may be due to its regulatory effects on T cells.

Administration, Inhalation↗
PubMed2006

GM1 binding-deficient exotoxin is a potent noninflammatory broad spectrum intradermal immunoadjuvant.

Intradermal (i.d.) immunization is a promising route of vaccine administration. Suitable i.d. adjuvants are important to increase vaccine efficacy in poorly responding populations such as the elderly or for dose-sparing strategies in the face of vaccine shortages. Bacterial exotoxins, such as Escherichia coli heat-labile enterotoxin (LT), exert strong immunostimulatory effects through binding to monosialoganglioside (GM1) cell surface receptors; however, injection is hampered by local inflammation. We demonstrate that the injection of LT formulations deficient in GM1 binding by mutation (LT(G33D)) or in vitro ligand coupling does not cause localized edema and inflammation in mice, yet these formulations retain potent adjuvant activity by enhancing functional Ab and cellular immune responses to coadministered Ags. Complete protection against in vivo lethal tetanus toxin challenge and the induction of Ag-specific CTL responses capable of killing target cells in vivo indicated in vivo efficacy of the induced immune responses. LT(G33D) proved superior to standard alum adjuvant regarding the magnitude and breadth of the induced immune responses. Immunizations in complex ganglioside knockout mice revealed a GM1-independent pathway of LT adjuvanticity. Immunostimulation by i.d. LT(G33D) is explained by its ability to induce migration of activated APCs to the proximal draining lymph nodes. LT(G33D) is a promising candidate adjuvant for human trials of parenteral vaccines in general and for current i.d. vaccine development in particular.

Adjuvants, Immunologic↗
PubMed2001

Antiaggregation effect of alum on human platelets.

OBJECTIVE: The purpose of this study was to evaluate the effect of alum on human platelet aggregation. METHODS: Platelet-rich plasma fractions were prepared from fresh blood drawn from a group of healthy male volunteers. Platelet aggregation was induced by various inducers. The percent aggregation was recorded in the absence and presence of various concentrations of alum. RESULTS: Alum at concentrations less than 1.5 mg/ml inhibited platelet aggregation induced by collagen, epinephrine. ADP and thrombin in a dose-dependent manner. The IC50s were 0.668, 0.324, 0.250 and 0.191 mg/ml of alum, for collagen-, epinephrine-, ADP- and thrombin-induced platelet aggregation, respectively. In contrast, alum at concentrations up to 1.5 mg/ml did not inhibit ristocetin-induced platelet aggregation. CONCLUSION: Alum has an anti-platelet action and should be used cautiously in the treatment of intractable intravesical hemorrhage. Alum is a cheap anti-platelet drug that needs further investigation.

Adjuvants, Immunologic↗
PubMed1980

Stingose.

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Alum Compounds↗
PubMed1980

Stingose.

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Alum Compounds↗
PubMed1985

IgE antibody against hepatitis B surface antigen in mice.

Hepatitis B surface antigen (HBs antigen) was examined for elicitation of IgE production by injection into mice. The Prausnitz-Küstner (PK)-type skin test in the rat was employed for detection of IgE antibody to HBs antigen, because no sufficient purified HBs antigen was available as the challenging antigen for the passive cutaneous anaphylaxis (PCA) test in rats. The positive PK test was considered to be due to IgE antibody, since the active principle was inactivated by heating the sera at 56 C for 30 min, did not bind to protein A and was eliminated by anti-mouse IgE antisera. These data indicate that the PK-type test in rats can be used for detection of mouse IgE antibody when the amount of a test sample is not sufficient for the PCA test in rats.

Adjuvants, Immunologic↗
PubMed1999

Adjuvant-guided type-1 and type-2 immunity: infectious/noninfectious dichotomy defines the class of response.

Traditionally, protein Ags have been injected in CFA (oil with inactivated mycobacteria) to induce immunity and with IFA (oil alone) to induce tolerance. We report here that injection of hen eggwhite lysozyme, a prototypic Ag, in CFA-induced and IFA-induced pools of hen eggwhite lysozyme-specific memory T cells of comparable fine specificity, clonal size, and avidity spectrum, but with type-1 and type-2 cytokine signatures, respectively. This adjuvant-guided induction of virtually unipolar type-1 and type-2 immunity was observed with seven protein Ags and in a total of six mouse strains. Highly polarized type-1 and type-2 immunity are thus readily achievable through the choice of adjuvant, irrespective of the genetic bias of the host and of the nature of the protein Ag. This finding should have far-reaching implications for the development of vaccines against infectious and autoimmune diseases. Furthermore, our demonstration that Ag injected with IFA is as strongly immunogenic for T cells as it is with CFA shows that the presence of the mycobacteria determines not the priming of naive T cells through the second-signal link but the path of downstream differentiation toward CD4 memory cells that express either type-1 or type-2 cytokines.

Alum Compounds↗
PubMed1998

Influence of aluminium on erythropoiesis, iron metabolism and some functional characteristics of erythrocytes in rats.

The increased aluminium (Al) levels in serum of patients with chronic renal failure on hemodialysis are associated with impaired erythropoiesis and iron metabolism. The long term Al loading of rats (20 to 90 days) has similar effect. Data are still lacking about the effects after short-term aluminium treatment. The 7 day's treatment with Al2(SO4)3 in a dose 67.5 mg/kg b. w., i. m. m. significantly decreased hemoglobin, hematocrit, incorporation of 59Fe in newly formed erythrocytes and increased reticulocytes in absolute and relative counts. We observed a mild degree hypochromic, ferropenic, microcytic anemia and polychromazia in the available macrocytes. The immature erythroblasts were predominant forms in the erythroblastogram while the number of mature erythroblasts was decreased. Index of maturation of erythroblasts was lower, indicating inhibited erythroblast maturation. Plasma iron, TIBC, transferrin saturation and 59Fe absorption in the experimental group were significantly decreased. Spontaneous and mechanical hemolysis of erythrocytes were lower while erythrocyte deformability was increased. Obviously, Al treatment inhibits erythropoiesis and iron metabolism, probably hinders hemoglobin synthesis and erythroid cell maturation but does not affect the studied functional characteristics of mature erythrocytes negatively.

Alum Compounds↗
PubMed1999

Humoral response suppression observed with CD23 transgenics.

CD23, also known as the low affinity IgE receptor (FcepsilonRII), has been hypothesized to have a role in IgE regulation. A new CD23 transgenic mouse was generated using the MHC class I promoter and IgH enhancer to further test the hypothesis that CD23 plays a role in the down-regulation of IgE. Study of three founder lines by FACS showed overexpression to varying extents on both B and T lymphocytes. No alterations in lymphocyte populations was observed. All three founder lines exhibited strong suppression of IgE in response to DNP-keyhole limpet hemocyanin/alum and Nippostrongylus brasiliensis infection compared with that in parental or littermate controls. The founder line exhibiting the highest level of suppression also was less susceptible to Ag-induced systemic anaphylactic shock. Overall, the data support the concept that enhancing CD23 levels can be used to suppress IgE-mediated disease. The mechanism involves decreased IgE synthesis, because the serum half-life of IgE was not altered in transgenics, and enzyme-linked immunospot analysis demonstrated lower IgE-producing cells stimulated by injection of anti-IgD. Transgenics also exhibited significantly decreased IgG1 responses and exhibited lower levels of all Ig isotypes, although this was more variable in different founder lines.

Alum Compounds↗
PubMed1998

Effects of aluminum potassium sulfate on learning, memory, and cholinergic system in mice.

AIM: To study the relationship between aluminum potassium sulfate (APS) and memory deficits of mice. METHODS: 30, 60, or 90 d after the mice were given daily APS i.g., the step-through latency (STL) was determined with a passive avoidance task. Aluminum (Al) contents in brain and blood were assayed with atomic absorption spectrophotometry. Acetylcholine (ACh) content in brain was determined with chemiluminescent method and choline acetyltransferase (ChAT) activity was measured radiochemically. RESULTS: APS 1 g.kg-1 increased blood-Al only after 30 d. After 60 d, STL, ACh content and ChAT activity decreased by 46.4%, 8.5%, and 22.6%, respectively. These parameters decreased by 50%, 11.1%, and 27.8%, respectively, with increased Al in blood and brain, after 90 d. APS 0.25 g.kg-1 had no effects on mice except blood-Al. In ethylcholine mustard aziridium chloride (AF64A) treated mice, APS 1 g.kg-1 only increased blood and brain-Al. CONCLUSION: The intake of APS 1 g.kg-1.d-1 for 60 d induced learning and memory deficits in mice.

Acetylcholine↗
PubMed1999

Protective immunity using recombinant human IL-12 and alum as adjuvants in a primate model of cutaneous leishmaniasis.

Protection from cutaneous leishmaniasis, a chronic ulcerating skin lesion affecting millions, has been achieved historically using live virulent preparations of the parasite. Killed or recombinant Ags that could be safer as vaccines generally require an adjuvant for induction of a strong Th1 response in murine models. Murine rIL-12 as an adjuvant with soluble Leishmania Ag has been shown to protect susceptible mice. We used 48 rhesus macaques to assess the safety, immunogenicity, and efficacy of a vaccine combining heat-killed Leishmania amazonensis with human rIL-12 (rhIL-12) and alum (aluminum hydroxide gel) as adjuvants. The single s.c. vaccination was found to be safe and immunogenic, although a small transient s.c. nodule developed at the site. Groups receiving rhIL-12 had an augmented in vitro Ag-specific IFN-gamma response after vaccination, as well as increased production of IgG. No increase in IL-4 or IL-10 was found in cell culture supernatants from either control or experimental groups. Delayed hypersensitivity reactions were not predictive of protection. Intradermal forehead challenge infection with 107 metacyclic L. amazonensis promastigotes at 4 wk demonstrated protective immunity in all 12 monkeys receiving 2 microgram rhIL-12 with alum and Ag. Partial efficacy was seen with lower doses of rhIL-12 and in groups lacking either adjuvant. Thus, a single dose vaccine with killed Ag using rhIL-12 and alum as adjuvants was safe and fully effective in this primate model of cutaneous leishmaniasis. This study extends the murine data to primates, and provides a basis for further human trials.

Adjuvants, Immunologic↗
PubMed1975

[Management of gingival inflammation with active ingredients in toothpaste].

In order to study the effect of active additives in toothpastes, three different toothpastes were tested in 60 persons for a period of four weeks. The toothpastes used contained allantoin, pyridyl carbinol, alpha-tocopherol, potassium aluminum sulfate, and tartaric acid. In addition, a control paste without additives was used. In a double blind study plaque incidence of the Ramfjord teeth was determined by means of the indices of Silness and Löe and Quigley and Hein. The tissue reactions were studied by means of the S-B index and the keratinization index. After an initial examination for extablishing the origianl values, the indices were determined after 2 and 4 weeks. Statistical analysis of the data obtained allows the conclusion that none of the tested active additives in the concentrations applied had any applied had any medicamentous influence on the gingival inflammation. The therapeutical consequences are discussed.

Administration, Topical↗