Developmental Immunotoxicity in Rodents

Dietert, Rodney R.; Burns‐Naas, Leigh Ann

doi:10.1002/9780470386385.ch21

Cited by 4 publications

(12 citation statements)

References 66 publications

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“…Some key considerations for inclusion of endpoints on DIT studies are: (i) that some functional endpoints have sub-optimal activity in the developing immune system; (ii) sample sizes and volumes may impact the age at which the endpoints can optimally be evaluated; and (iii) lack of historical data in developing animals. Measuring multiple immunotoxicity parameters can be important in interpreting the biological or clinical significance of observed changes Dietert and Holsapple, 2007;Dietert and Burns-Naas, 2008). The most common endpoints used to evaluate the effects of drugs on the developing immune system are discussed below.…”

Section: Endpoint Selectionmentioning

confidence: 99%

“…The most common endpoints used to evaluate the effects of drugs on the developing immune system are discussed below. Other immune endpoints such as cytokine measurements are less well characterized (Bussiere, 2008a;Dietert and Burns-Naas, 2008). The choice of DIT endpoints to be evaluated should be based on a scientific rationale.…”

Section: Endpoint Selectionmentioning

confidence: 99%

“…Evidence of toxicity to the immune system would likely be evaluated with respect to the criteria outlined by Germolec (2009), which include demonstration that an effect on one or more immune parameters is dose-related when the magnitude of the effect and the dose-response are also considered, and is not secondary to systemic toxic effects. However, the predictivity of pathology in DIT is far less established (Dietert and Burns-Naas, 2008). With this caution in mind, pathology endpoints can be used as an initial screen to assess DIT.…”

Section: Immunopathologymentioning

confidence: 99%

“…For the most robust assessment of DIT, combining immunopathology with an examination of humoral immunity (e.g., TDAR) and an evaluation of cellular immunity such as the delayed-type hypersensitivity response (DTH), cytotoxic T-lymphocyte (CTL) response, or natural killer (NK) cell assay would appear to provide the broadest assessment of immunocompetence (Holsapple et al, 2004;Dietert and Holsapple, 2007;Burns-Naas et al, 2008, Dietert and. However, it is not recommended that functional endpoints always be included in assessments of DIT.…”

Section: Immune Function Testsmentioning

confidence: 99%

“…The TDAR assay may be valuable in evaluating the effects of drug candidates on the developing immune system (Dietert and Burns-Naas, 2008). In the rat, antibody responses to sheep red blood cells (SRBC) are sub-optimal at PND 21 (weaning).…”

Section: T-dependent Antibody Response (Tdar)mentioning

confidence: 99%

See 4 more Smart Citations

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

Collinge

Burns‐Naas

Chellman³

et al. 2012

Journal of Immunotoxicology

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Section: Endpoint Selectionmentioning

confidence: 99%

Section: Endpoint Selectionmentioning

confidence: 99%

Section: Immunopathologymentioning

confidence: 99%

Section: Immune Function Testsmentioning

confidence: 99%

Section: T-dependent Antibody Response (Tdar)mentioning

confidence: 99%

See 3 more Smart Citations

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

Collinge

Burns‐Naas

Chellman³

et al. 2012

Journal of Immunotoxicology

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Immunotoxicology

Burns‐Naas¹,

Pallardy²

2013

Nonclinical Safety Assessment

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Developmental immunotoxicology (DIT): windows of vulnerability, immune dysfunction and safety assessment

Dietert

2008

Journal of Immunotoxicology

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Developmental immunotoxicity (DIT) is an increasing health concern since DIT outcomes predispose children to those diseases that have been on the rise in recent decades (e.g., childhood asthma, allergic diseases, autoimmune conditions, childhood infections). The enhanced vulnerability of the developing immune system for environmental insult is based on unique immune maturational events that occur during critical windows of vulnerability in early life. The semi-allogeneic pregnancy state, with suppression of graft rejection and associated skewing of the fetal and neonatal immune system, also influences the specific nature of DIT outcomes. In the exposed offspring, targeted immunosuppression can co-exist with an increased risk of allergic and/or autoimmune disease. Because with DIT immune dysfunction rather than profound immunosuppression is the greater concern, testing approaches should emphasize multi-functional assessment. Beyond T-cells, dendritic cells and macrophages are sensitive targets. The last-trimester fetus and the neonate are normally depressed in T(H)1-dependent functions and postnatal acquisition of needed T(H)1 capacity is a major concern with DIT. With this in mind, assessment should include a measure of T(H)1-dependent cell-mediated immunity [cytotoxic T-lymphocyte (CTL) activity or delayed-type hypersensitivity (DTH) response] in conjunction with a multi-isotype T-dependent antibody response (TDAR) and evaluation of innate immunity (e.g., NK activity). Other parameters such as immune histology, immunophenotyping, cytokine responses, and organ weights can be useful when included with immune functional evaluation. A multifunctional DIT protocol using influenza challenge is presented as one example of an approach that permits dysfunction and misregulation to be evaluated.

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Developmental Immunotoxicity in Rodents

Cited by 4 publications

References 66 publications

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

Immunotoxicology

Developmental immunotoxicology (DIT): windows of vulnerability, immune dysfunction and safety assessment

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