Overview of in vitro assessment of immunotoxicity

Corsini, Emanuela; Roggen, Erwin

doi:10.1016/j.cotox.2017.06.016

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…The use of in vitro assays for immunotoxicity testing is most advanced in human toxicology. Currently, immunotoxicity testing in human toxicology relies on animal tests, which include general immune endpoints in repeated dose studies and trigger-based tests on a case-by-case basis [e.g., (66)(67)(68)]. In the United States, the National Toxicology Program developed a tiered in vivo immunotoxicity testing strategy which includes tier I tests like the assessment of antigen-induced humoral immunity or cell-mediated immunity as well as general parameters like immune organ weight or histopathology (69).…”

Section: Assessing the Immunotoxic Activity Of Chemicals By In Vitro ...mentioning

confidence: 99%

“…Tier II includes, among others, tests on hypersensitivity or on the cytotoxic T cell response. A tiered strategy for in vitro immunotoxicity assessment could start with an evaluation of myelotoxicity, which examines whether the toxicant leads to a decreased production of bone marrow-derived immune progenitor cells ( 64 , 68 , 70 ). For this purpose, often the humane/murine clonogenic CFU-GM (Colony Forming Unit – Granulocyte Macrophage) test is used ( 71 ).…”

Section: Assessing the Immunotoxic Activity Of Chemicals By ...mentioning

confidence: 99%

“…If a compound is not myelotoxic, the following tiers assess the impact of the chemical on the viability and function of differentiated immune cells, mainly on lymphocytes. Initially, the overt cytotoxicity of the chemical towards immune cells is determined, and then, using non-cytotoxic concentrations, the impacts on selected cell functions are tested, for instance, cytokine production or lymphocyte proliferation assays ( 64 , 68 , 70 ). The function tests include also genetically modified reporter gene cell systems like the “fluorescent cell chip” ( 72 ) or the IL-2 luciferase assay ( 73 ).…”

Section: Assessing the Immunotoxic Activity Of Chemicals By ...mentioning

confidence: 99%

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Assessing Fish Immunotoxicity by Means of In Vitro Assays: Are We There Yet?

Segner

Rehberger

Bailey³

et al. 2022

Front. Immunol.

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There is growing awareness that a range of environmental chemicals target the immune system of fish and may compromise the resistance towards infectious pathogens. Existing concepts to assess chemical hazards to fish, however, do not consider immunotoxicity. Over recent years, the application of in vitro assays for ecotoxicological hazard assessment has gained momentum, what leads to the question whether in vitro assays using piscine immune cells might be suitable to evaluate immunotoxic potentials of environmental chemicals to fish. In vitro systems using primary immune cells or immune cells lines have been established from a wide array of fish species and basically from all immune tissues, and in principal these assays should be able to detect chemical impacts on diverse immune functions. In fact, in vitro assays were found to be a valuable tool in investigating the mechanisms and modes of action through which environmental agents interfere with immune cell functions. However, at the current state of knowledge the usefulness of these assays for immunotoxicity screening in the context of chemical hazard assessment appears questionable. This is mainly due to a lack of assay standardization, and an insufficient knowledge of assay performance with respect to false positive or false negative signals for the different toxicant groups and different immune functions. Also the predictivity of the in vitro immunotoxicity assays for the in vivo immunotoxic response of fishes is uncertain. In conclusion, the currently available database is too limited to support the routine application of piscine in vitro assays as screening tool for assessing immunotoxic potentials of environmental chemicals to fish.

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Section: Assessing the Immunotoxic Activity Of Chemicals By In Vitro ...mentioning

confidence: 99%

Section: Assessing the Immunotoxic Activity Of Chemicals By ...mentioning

confidence: 99%

Section: Assessing the Immunotoxic Activity Of Chemicals By ...mentioning

confidence: 99%

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Assessing Fish Immunotoxicity by Means of In Vitro Assays: Are We There Yet?

Segner

Rehberger

Bailey³

et al. 2022

Front. Immunol.

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“…Although they cannot provide a definitive assessment of adverse immune effects, they can screen potential immunotoxic activities and prioritize positive compounds for further testing (e.g. 40 , 41 , 43 , 44 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of an in vitro assay to screen for the immunotoxic potential of chemicals to fish

Rehberger

Escher

Scheidegger

et al. 2021

Sci Rep

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A wide variety of environmental contaminants has been shown to disrupt immune functions of fish and may compromise their defense capability against pathogens. Immunotoxic effects, however, are rarely considered in ecotoxicological testing strategies. The aim of this study was to systematically evaluate the suitability of an in vitro immuno-assay using selected fish immune parameters to screen for chemicals with known immunotoxic potential and to differentiate them from non-immunotoxicants. Non-stimulated and lipopolysaccharide-stimulated head kidney leukocytes of rainbow trout (Oncorhynchus mykiss) were exposed for 3 h or 19 h to chemicals with different modes of action. As immune parameters, phagocytosis activity, oxidative burst activity and cytokine transcription (IL-1β, TNFα, IL-10) were examined, accompanied by in silico modelling. The immunotoxicants dexamethasone, benzo(a)pyrene, ethinylestradiol and bisphenol A significantly altered the immune parameters at non-cytotoxic concentrations whereas diclofenac had only weak effects. However, the two baseline chemicals with no known immunotoxic potential, butanol and ethylene glycol, caused significant effects, too. From our results it appears that the in vitro fish leukocyte assay as performed in the present study has only a limited capacity for discriminating between immunotoxicants and non-immunotoxicants.

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“…oxidative stress, depletion of antioxidants and induction of apoptosis, may lead to different outcomes depending on the sensitivity of each cell type to the different mechanisms (De La Fuente et al, 2002;Tsangaris & Tzortzatou-Stathopoulou, 1998). Different cell targets and toxic mechanisms that lead to adverse outcomes, such as immunosuppression, can be targeted using in vitro methods to determine representative biomarkers for immunotoxicological assessment (Corsini & Roggen, 2017). To elucidate cell type-specific toxicity, this study was carried out using murine macrophage and mast cell in vitro models and cadmium as a model compound, because of its potential immunomodulatory effects.…”

Section: Introductionmentioning

confidence: 99%

Cell‐specific immune‐modulation of cadmium on murine macrophages and mast cell lines in vitro

García-Mendoza

Han

Berg

et al. 2019

J of Applied Toxicology

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Toxic trace metals are widespread contaminants that are potentially immunotoxic even at environmentally low exposure levels. They can modulate the immunity to infections, e.g., in wildlife species living in contaminated areas. The diverse immune cell types can be differentially affected by the exposure leading to the modulation of specific protective mechanisms. Macrophages and mast cells, part of the innate immune system, trigger immune responses and perform particular effector functions. The present study compared toxicological and functional effects of cadmium in two models of murine macrophages (RAW264.7 and NR8383 cell lines) and two models of murine mast cells (MC/9 and RBL‐2H3 cell lines). Cadmium was selected as a model compound because its known potential to induce reactive oxygen species and its relevance as an environmental contaminant. Mechanisms of toxicity, such as redox imbalance and apoptosis induction were measured in stationary cells, while functional outcome effects were measured in activated cells. Cadmium‐depleted glutathione antioxidant in all four cell lines tested although reactive oxygen species was not significantly increased. Mast cells had full dose‐response depletion of glutathione below cytotoxic levels while in macrophages the depletion was not complete. Functional endpoints tumour necrosis factor‐alpha and nitrite production in lipopolysaccharide‐activated macrophages were increased by cadmium exposure. In contrast, mast cell lipopolysaccharide‐induced tumour necrosis factor‐alpha and IgE‐mediated histamine release were reduced by cadmium. These data indicate potentially differential effects of cadmium among murine innate immune cell types, where mast cells would be more susceptible to oxidative stress and their function might be at a higher risk to be modulated compared to macrophages.

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Overview of in vitro assessment of immunotoxicity

Cited by 13 publications

References 39 publications

Assessing Fish Immunotoxicity by Means of In Vitro Assays: Are We There Yet?

Assessing Fish Immunotoxicity by Means of In Vitro Assays: Are We There Yet?

Evaluation of an in vitro assay to screen for the immunotoxic potential of chemicals to fish

Cell‐specific immune‐modulation of cadmium on murine macrophages and mast cell lines in vitro

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