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  • How aluminum adjuvants could promote and enhance non-target IgE synthesis in a genetically-vulnerable sub-population.

How aluminum adjuvants could promote and enhance non-target IgE synthesis in a genetically-vulnerable sub-population.

Journal of immunotoxicology (2012-09-13)
Todd D Terhune, Richard C Deth
摘要

Aluminum-containing adjuvants increase the effectiveness of vaccination, but their ability to augment immune responsiveness also carries the risk of eliciting non-target responses, especially in genetically susceptible individuals. This study reviews the relevant actions of aluminum adjuvants and sources of genetic risk that can combine to adversely affect a vulnerable sub-population. Aluminum adjuvants promote oxidative stress and increase inflammasome activity, leading to the release of IL-1β, IL-18, and IL-33, but not the important regulatory cytokine IL-12. In addition, they stimulate macrophages to produce PGE₂, which also has a role in regulating immune responses. This aluminum-induced cytokine context leads to a T(H)2 immune response, characterized by the further release of IL-3, IL-4, IL-5, IL-9, IL-13, and IgE-potentiating factors such as sCD23. Genetic variants in cytokine genes, such as IL-4, IL-13, IL-33, and IL-18 influence the response to vaccines in children and are also associated with atopy. These genetic factors may therefore define a genetically-vulnerable sub-population, children with a family history of atopy, who may experience an exaggerated T(H)2 immune response to aluminum-containing vaccines. IL-4, sCD23, and IgE are common factors for both atopy and the immune-stimulating properties of aluminum adjuvants. IL-4 is critical in the production of IgE and total IgE up-regulation. IL-4 has also been reported to induce the production of sCD23 and trigger resting sIgM+, sIgD+ B-cells to switch to sIgE+ B-cells, making them targets for IgE-potentiating factors. Further, the actions of IgE-potentiating factors on sIgE+ B-cells are polyclonal and unrestricted, triggering their differentiation into IgE-forming plasma cells. These actions provide a mechanism for aluminum-adjuvant promotion and enhancement of non-target IgE in a genetically vulnerable sub-population. Identification of these individuals may decrease the risk of adverse events associated with the use of aluminum-containing vaccines.

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铝, foil, thickness 0.45-0.55 mm, 99.999% trace metals basis
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铝, granular, <1 mm, 99.7% trace metals basis
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铝, wire, diam. 1.0 mm, 99.999% trace metals basis
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铝, ReagentPlus®, beads, 5-15 mm, 99.9% trace metals basis
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铝, foil, thickness 0.25 mm, 99.999% trace metals basis
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铝, pellets, 3-12 mm, 99.99% trace metals basis
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铝, evaporation slug, diam. × L 6.3 mm × 6.3 mm, 99.999% trace metals basis
Sigma-Aldrich
铝, wire, diam. 0.58 mm, ≥99.99% trace metals basis
Sigma-Aldrich
铝, ≤30 μm, spherical powder, ≥99%
Sigma-Aldrich
铝, foil, thickness 0.13 mm, ≥99.99% trace metals basis
Sigma-Aldrich
铝, pellets, 3-8 mesh, ≥99.999% trace metals basis
Sigma-Aldrich
铝, ACS reagent, 99%, wire, wire diam. ~1.5 mm
Sigma-Aldrich
铝, rod, diam. × L 3.0 mm × 100 mm, 99.999% trace metals basis
铝, IRMM®, certified reference material, 0.1 mm foil
铝, wire reel, 25m, diameter 0.25mm, as drawn, 99.5%
铝, wire reel, 10m, diameter 0.025mm, as drawn, 99.0+%
铝, honeycomb, 300x300mm, thickness 5mm, cell size 3.2mm, cell wall 0.025mm, core density 0.072g/cm3, phenolic adhesive (resin), 99.5%
铝, wire reel, 500m, diameter 0.5mm, as drawn, 99.5%
铝, mesh, 150x150mm, nominal aperture 0.38mm, wire diameter 0.25mm, 40x40 wires/inch, open area 37%, plain weave mesh
铝, foam, 150x150mm, thickness 10mm, bulk density 0.2g/cm3, porosity 0.93, aluminum 6101 grade, 98.5%
铝, foam, 150x150mm, thickness 3.2mm, bulk density 0.2g/cm3, porosity 0.93, 16 pores/cm, aluminum 6101 grade, 98.5%
铝, foam, 150x150mm, thickness 30mm, bulk density 0.2g/cm3, porosity 0.93, aluminum 6101 grade, 98.5%
铝, foam, 150x150mm, thickness 6.35mm, bulk density 0.2g/cm3, porosity 0.93, 16 pores/cm, aluminum 6101 grade, 98.5%
铝, foam, 150x150mm, thickness 6.35mm, bulk density 0.2g/cm3, porosity 0.93, 2 pores/cm, aluminum 6101 grade, 98.5%
铝, foam, 150x150mm, thickness 6.35mm, bulk density 0.2g/cm3, porosity 0.93, 4 pores/cm, aluminum 6101 grade, 98.5%
铝, foam, 150x150mm, thickness 6.35mm, bulk density 0.2g/cm3, porosity 0.93, 8 pores/cm, aluminum 6101 grade, 98.5%
铝, foam, 300x400mm, thickness 6.35mm, bulk density 0.2g/cm3, porosity 0.93, aluminum 6101 grade, 98.5%
铝, foam, 33x140mm, thickness 20mm, bulk density 0.2g/cm3, porosity 0.93, aluminum 6101 grade, 98.5%
铝, honeycomb, 150x150mm, thickness 10mm, cell size 3.2mm, cell wall 0.025mm, core density 0g/cm3, phenolic adhesive (resin), 99.5%
铝, honeycomb, 150x150mm, thickness 52.3mm, cell size 6.3mm, cell wall 0.064mm, core density 0.083g/cm3, phenolic adhesive (resin), facing skin aluminum 0.55mm, 99.9%

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