Multidimensional Immunomodulation

House, Robert V.; Hastings, Kenneth L.

doi:10.1080/15476910490503646

Cited by 14 publications

(3 citation statements)

References 35 publications

(28 reference statements)

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“…While vaccines are clearly intended to produce benefits in humans and animals, paradoxically they could strictly be characterized as immunotoxicants, given that immunotoxicology can be defined as an agent that modulates a resting or nominal immune state in either a positive or negative manner (House and Hastings, 2004). In practical terms, vaccines are evaluated for immunomodulatory activity very early in development, limiting the possibility of adverse immune findings prior to human trials.…”

Section: Immunotoxicitymentioning

confidence: 99%

International Safety Regulations for Vaccine Development

House¹

2013

Nonclinical Safety Assessment

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Section: Immunotoxicitymentioning

confidence: 99%

International Safety Regulations for Vaccine Development

House¹

2013

Nonclinical Safety Assessment

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“…While it has long been recognized that toxicity to the immune response can take many forms, including adverse immunostimulation, this topic has generally not been as well-defined as immunosuppression (House and Hastings, 2004). Immunotoxicology IV brought together a diverse group of experts from industry, academia, and the government to examine the concept of Immunotoxicology resulting from either intentional or unintentional therapeutic treatments in humans.…”

mentioning

confidence: 99%

Immunotoxicology IV—Innovative Methods and Applications for Risk Assessment in Pharmaceutical Development: Introduction to the Conference

House¹

2008

Journal of Immunotoxicology

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“…The lack existing knowledge pertaining to the nanomaterial immunotoxocity is particularly concerning since toxicants may impact various components of the immune system following any exposure route. Moreover, as a carefully-regulated, continually-renewing system in which cells are constantly undergoing differentiation, proliferation, and self-renewal, the immune system serves as a particularly vulnerable target of toxic effects (71). Given this knowledge, characterization of nanomaterial immunotoxic potential and investigations into the impact of physico-chemical properties in this context are needed.…”

Section: Knowledge Gaps Regarding the Toxic Effects Of Nanomaterialsmentioning

confidence: 99%

Metal Nanomaterials: Immune Effects and Implications of Physicochemical Properties on Sensitization, Elicitation, and Augmentation of Allergic Disease

Roach¹

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The recent surge in incorporation of engineered metallic and metal oxide nanomaterials into consumer products and their corresponding use in occupational settings has raised concerns over their potential to induce material size-specific toxicological effects. Although metal nanomaterials have been shown to induce greater degrees of lung injury and inflammation than their larger metal counterparts, their size-related effects on the immune system and allergic disease remain largely unknown. This knowledge gap is particularly concerning since metals are common inducers of allergic contact dermatitis, occupational asthma, and allergic adjuvancy.Overall, more scientific knowledge exists regarding the potential for metal-containing nanomaterials to exacerbate allergic disease than to their potential to induce allergic disease. Furthermore, effects of metal nanomaterial exposure on respiratory allergy have been more thoroughly-characterized than their potential influence on dermal allergy. Despite the existence of such knowledge, specific correlations between metal nanomaterial physico-chemical properties and their allergic effects have yet to be consistently demonstrated. As the number of emerging nanomaterials continues to increase, the delineation of these relationships has the potential to advance risk assessment efforts by helping to identify specific agents that may present an elevated risk for allergic effects.Two sets of studies were designed to begin addressing some of the knowledge gaps associated with the immunotoxic potential of metal nanomaterials in the context of allergic disease. The hypothesis of these studies was that nanomaterials comprised of metal constituents with known immunomodulatory potential augment, induce, and elicit allergic disease more readily than larger forms of the materials. Moreover, the nature of the immune responses caused by exposure to these metal nanomaterials, as well as the magnitude of the effects, correlates best with the parameter of dose surface area.The first set of studies incorporated NiO particles with different physico-chemical properties into an in vivo time course study and OVA asthma model. Results from the time course study demonstrated that the smaller NiO particles caused more pronounced pulmonary injury and inflammation, a discrepancy that could be mitigated by normalizing the administered particle dose to the surface area of the larger material. In the OVA model, augmentation of the allergic response was largely conserved with respect to NiO surface area, wherein larger doses caused polarization of pulmonary immune reposes towards a Th1/17-dominant state and smaller doses induced Th2-skewed responses. Despite this association, several immune markers, including total IgE production, BAL eosinophil number, and Penh response correlated better with other metrics, such as particle size.The second set of studies employed Au particles and nanoparticles to assess size-specific differences in allergenic potential. Neither particle was associated with potential for skin...

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Multidimensional Immunomodulation

Cited by 14 publications

References 35 publications

International Safety Regulations for Vaccine Development

International Safety Regulations for Vaccine Development

Immunotoxicology IV—Innovative Methods and Applications for Risk Assessment in Pharmaceutical Development: Introduction to the Conference

Metal Nanomaterials: Immune Effects and Implications of Physicochemical Properties on Sensitization, Elicitation, and Augmentation of Allergic Disease

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