Developmental Immunotoxicity (DIT): Assays for Evaluating Effects of Exogenous Agents on Development of the Immune System

2012 ◽  
Vol 51 (1) ◽  
Author(s):  
Jamie C. DeWitt ◽  
Margie M. Peden‐Adams ◽  
Deborah E. Keil ◽  
Rodney R. Dietert
Keyword(s):  
Immune System ◽  
Exogenous Agents ◽  
Developmental Immunotoxicity

Developmental immunotoxicology and risk assessment: a workshop summary

2002 ◽  
Vol 21 (9-10) ◽  
pp. 473-478 ◽  
Author(s):  
M P Holsapple
Keyword(s):  
Risk Assessment ◽  
Immune System ◽  
Environmental Protection Agency ◽  
Standard Procedure ◽  
Panel Discussion ◽  
Chemical Exposure ◽  
Technical Committee ◽  
Individual Species ◽  
Standard Practices ◽  
Developmental Immunotoxicity

A workshop entitled ‘Developmental Immunotoxicology and Risk Assessment’ was held on 12–13 June 2001, in Washington, DC. The workshop was organized jointly by the Immunotoxicology Technical Committee (ITC) of the International Life Sciences Institute's (ILSI) Health and Environmental Sciences Institute (HESI) with input from the U.S. Environmental Protection Agency (EPA). Growing public concern that early exposure of the developing immune system to immunotoxic compounds may cause significant or persistent postnatal immunosuppression prompted the workshop. The main goal of the workshop was to examine scientific questions that underlie developmental immunotoxicity tests and the interpretation of the results as they relate to human risk assessment. A second goal was to provide a framework, based on current scientific knowledge, for the development of meaningful testing guidelines. The workshop focused on a series of questions that included how to address critical windows of exposure, how to develop and apply more predictive endpoints, does early chemical exposure cause transient or permanent effects on the immune system, as well as other related questions. On the first day, experts were invited to give scientific presentations relating to comparative developmental immunology, models of immunosuppression, and the regulatory aspects of developmental immunotoxicology. The second day was devoted to a panel discussion that included all the speakers as well as meeting participants, which attempted to answer each of the specific questions raised at the workshop. In general, it was acknowledged that there are a variety of techniques available for assessing immunosuppression in adult animal models, but there is uncertainty about how to apply these to a developing animal, especially if the goal is to have some standard procedure that can be applied for regulatory risk assessment. It was pointed out that although we know a lot about the developing immune system of individual species, we do not know how to relate the significance of drug or chemical effects on these systems in terms of human hazard. Overall, the panel deemed the area of developmental immunotoxicity to be still in its infancy and outlined strategies that could lead to the development of standard practices.

What’s So Special about the Developing Immune System?

2008 ◽  
Vol 27 (2) ◽  
pp. 223-254 ◽  
Author(s):  
Leigh Ann Burns-Naas ◽  
Kenneth L. Hastings ◽  
Gregory S. Ladics ◽  
Susan L. Makris ◽  
George A. Parker ◽  
...  
Keyword(s):  
Immune System ◽  
Toxicity Testing ◽  
Life Stages ◽  
Significant Progress ◽  
Immune Development ◽  
Immune Parameters ◽  
Current State ◽  
State Of The Science ◽  
Developmental Immunotoxicity ◽  
Nonhuman Species

The evolution of the subdiscipline of developmental immunotoxicology (DIT) as it exists today has been shaped by significant regulatory pressures as well as key scientific advances. This review considers the role played by legislation to protect children’s health, and on the emergence of immunotoxcity and developmental immunotoxicity guidelines, as well as providing some context to the need for special attention on DIT by considering the evidence that the developing immune system may have unique susceptibilities when compared to the adult immune system. Understanding the full extent of this potential has been complicated by a paucity of data detailing the development of the immune system during critical life stages as well as by the complexities of comparisons across species. Notably, there are differences between humans and nonhuman species used in toxicity testing that include specific differences relative to the timing of the development of the immune system as well as more general anatomic differences, and these differences must be factored into the interpretation of DIT studies. Likewise, understanding how the timing of the immune development impacts on various immune parameters is critical to the design of DIT studies, parameters most extensively characterized to date in young adult animals. Other factors important to DIT, which are considered in this review, are the recognition that effects other than suppression (e.g., allergy and autoimmunity) are important; the need to improve our understanding of how to assess the potential for DIT in humans; and the role that pathology has played in DIT studies in test animals. The latter point receives special emphasis in this review because pathology evaluations have been a major component of standard nonclinical toxicology studies, and could serve an important role in studies to evaluate DIT. This possibility is very consistent with recommendations to incorporate a DIT evaluation into standard developmental and reproductive toxicology (DART) protocols. The overall objective of this review is to provide a ‘snapshot’ of the current state-of-the-science of DIT. Despite significant progress, DIT is still evolving and it is our hope that this review will advance the science.

Critical windows in development of the rodent immune system

2002 ◽  
Vol 21 (9-10) ◽  
pp. 493-498 ◽  
Author(s):  
K S Landreth
Keyword(s):  
Stem Cells ◽  
Immune System ◽  
Chemical Exposure ◽  
Anatomical Location ◽  
Hematopoietic Stem ◽  
Windows Of Vulnerability ◽  
The Impact ◽  
Timing Of Exposure ◽  
Developmental Immunotoxicity ◽  
Developmental Windows

The immune system of rodents, like that in humans, develops from a population of pluripotential hematopoietic stem cells (HSC) that are generated early in gestation from uncommitted mesenchymal stem cells in the intra-embryonic splanchnoplure surrounding the heart. This early population of HSC gives rise to all circulating blood cell lineages, including cells of the innate and acquired immune system. To access the impact of chemical exposure on the developing immune system and establish developmental windows of potential vulnerability to these exposures, it is essential to first consider the anatomical development of hematopoietic and lymphopoietic tissues and the sequence of appearance of cells that give rise to the immune system. This is particularly true in embryonic development because, after they initially appear in intra-embryonic mesenchyme early in gestation, HSC migrate through an orderly series of tissues before establishing residence in the bone marrow and thymus. The effect of exposure to chemical insults in utero, then, may differ depending on the specific timing of exposure and anatomical location of hematopoiesis. Mechanisms and consequences of developmental immunotoxicity in experimental animals will need to be considered in that context. This review presents an overview of developmental hematopoiesis and a working hypothesis of critical developmental windows of vulnerability of this developmental system to toxic insult by chemical exposure.

The rat as a model in developmental immunotoxicology

2002 ◽  
Vol 21 (9-10) ◽  
pp. 513-519 ◽  
Author(s):  
R J Smialowicz
Keyword(s):  
Immune System ◽  
Aromatic Hydrocarbon ◽  
Immune Function ◽  
Organochlorine Pesticides ◽  
System Development ◽  
Environmental Chemicals ◽  
Adult Rats ◽  
Immune System Development ◽  
Developmental Immunotoxicity ◽  
Juvenile Development

Evidence is presented to demonstrate that the rat is a sensitive rodent species for developmental immunotoxicity testing of chemicals. A battery of immune function assays was performed in adult rats, which were exposed perinatally (i.e., during gestational, lactational, and//or juvenile development) to three different classes of environmental chemicals. The chemicals employed were the following: the organotins di-n-octyltindichloride (DOTC) and tributyltin oxide (TBTO); the polyhalogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); and the organochlorine pesticides methoxychlor (MXC) and heptachlor (HEP). Suppression of immune function was observed in adult rats exposed to each of these chemicals during immune system development. The duration of immune function suppression in the rats so exposed ranged from three weeks (i.e., DOTC and MXC) to 19 months (i.e., TCDD) after the last exposure to the chemical.

scholarly journals Teratogen-induced Decrements of Postnatal Functional Capacity

1986 ◽  
Vol 5 (6) ◽  
pp. 517-524
Author(s):  
L. M. Newman ◽  
E. M. Johnson
Keyword(s):  
Life Cycle ◽  
Immune System ◽  
Gastrointestinal Tract ◽  
Embryonic Development ◽  
Clinical Evaluation ◽  
Functional Capacity ◽  
Fetal Development ◽  
Present Report ◽  
Different Ages ◽  
Exogenous Agents

Differences in response to pharmacologic or other exogenous agents occur when they are applied to individuals of different ages. The present report presents a discussion of the relative vulnerabilities of various early stages in the life cycle. Various published results, using several systems, including lung, kidney, gastrointestinal tract, and immune system, have clearly established that unique developmental events take place not just in embryonic development but also during fetal development and that the latter period may be highly vulnerable to perturbation by a teratogenic agent. Defects may be manifest in subtle ways and result in neonates that, although they may appear to be normal, in fact lack physiologic reserves or capabilities beyond those necessary for simply surviving. In the clinical world, it is possible that a prenatal insult often undetected by routine types of clinical evaluation could put an individual at jeopardy or increase its postnatal vulnerability to an insult tolerated by unaltered off spring.

Learned Placebo Effects in the Immune System

2014 ◽  
Vol 222 (3) ◽  
pp. 148-153 ◽  
Author(s):  
Sabine Vits ◽  
Manfred Schedlowski
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Associative Learning ◽  
Placebo Response ◽  
Immunosuppressive Drug ◽  
Immune Functions ◽  
Placebo Effects ◽  
New Therapeutic Approaches ◽  
Biological Variables ◽  
Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

Sign in / Sign up

Export Citation Format

Share Document