compounds introduced into the environment by human activity have
the potential to disturb the immune system of wildlife and humans.
The consequences of such interference on the developing immune system
are not well understood. Because of the pervasive contamination
of the environment by compounds with such activity, a multidisciplinary
group of experts gathered in retreat
at Wingspread, Racine, Wisconsin, 10-12 February 1995, to assess
what is known about the issue. Participants included experts in
the fields of biology, ecology, economy, comparative immunology,
medicine, microbiology, neurobiology, toxicology, veterinary medicine,
virology, wildlife biology and zoology.
purposes of the meeting were a) to reach agreement in principle
on the magnitude and scope of the problem of exposure to synthetic
chemicals on the immune systems of wildlife and humans, with a special
emphasis on development; b) to identify the conclusions that can
be drawn with confidence from the existing data; and c) to establish
a research agenda that would clarify uncertainties that need to
following consensus was reached by participants at the workshop.
We are certain of the following:
We estimate with confidence that-
competent immune system is essential for health.
lab studies demonstrate that certain synthetic chemicals affect
the immune system (e.g., aromatic hydrocarbons; carbamates; heavy
metals; organohalogens; organophosphates; organotins; oxidant
air pollutants, such as ozone and nitrogen dioxide; and polycyclic
aromatic hydrocarbons). These effects are manifested as alterations
in the immune system that may lead to a decreased quality of life.
These alterations include immune modulation expressed as an increase
or decrease in measured immune parameters, hypersensitivity, and
in the characteristics of the immune system in humans and certain
wildlife species have been associated with both therapeutic and
environmental exposure to synthetic chemicals, e.g., diethylstilbestrol
(DES), dioxin, polychlorinated biphenyls (PCBs).
of the immune system can result from alterations in the development
of the immune system and may be long-lasting. The effects may
not be manifested at hatching or birth and may not be expressed
until the animal or human reaches adulthood.
capacity for immune response is determined early in development,
during prenatal and early postnatal development in mammals and
prehatching and early posthatching development in egg-laying species.
in the developing and mature immune systems may not be recognized
as an adverse health effect until long after exposure.
wildlife and human populations are exposed to elevated levels
of certain synthetic chemicals.
widespread exposure of populations of humans and wildlife to many
man-made chemicals has made it difficult, if not impossible, to
find control populations that have no exposure level. True control
populations for human and wildlife epidemiological studies are
based on our current understanding we predict-
synthetic chemicals, such as those listed above, released or reintroduced
into the environment act upon the developing and mature immune
systems in humans and other vertebrates.
and early postnatal mammals and the immature and early life stages
of amphibians, reptiles, fishes and birds are likely to be the
most vulnerable life stages to immunomodulation.
among exposure varies among gender, species and stages of the
life cycle. In addition to embryos, fetuses and the newborn, children,
the very old, and certain populations (e.g., chronically ill,
poorly nourished, HIV positive) are also likely to be more at
certain instances, humans and wildlife are experiencing immune
alterations. Data suggest that immune alterations seen in wild
animals and humans are consistent with those produced by synthetic
chemicals identified as immunotoxic in studies with laboratory
effects expressed in individuals could therefore be expressed
at the population level thus affecting biodiversity at the community
or ecosystem level.
system effects reported in wildlife, in parallel with in vitro
and in vivo experimental studies, support the possibility for
qualitative prediction of human effects.
predictive capability for immunomodulation is limited to identification
of qualitative changes not quantitative changes.
There are uncertainties in our understanding because-
synthetic chemicals can cause alterations of the developing immune
in immunologic function whether occurring prenatally or embryologically
or later in life can translate into altered host resistance and
susceptibiltiy to disease, including autoimmune disease. Disease
patterns are thus likely to be affected by immune modulation induced
by immunological toxicants.
Our judgment is that-
needs to be learned about how the immune system develops.
well-controlled human or wildlife ecoepidemiological studies that
document immune modulation have been completed.
lack of sensitive tests and the uncertainty about exposure have
been impediments in many of these studies. Exposure is well known
for some wildlife speices.
is known about the effects of exposure to chemical mixtures. Most
published studies use single agents when testing for the effects
of environmental exposure. The specific components of environmental
mixtures are rarely defined.
pharmacokinetics of many immunotoxic compounds in target organs
is understood in experimental animals but not in humans and wildlife.
are lacking about the persistence of the effects of immunomodulators.
regulatory purposes, the current lack of knowledge about the mechanisms
leading to immunomodulation makes cause-and-effect linkages extremely
exists about whether the right questions have been asked concerning
the mechanisms of immune modulation.
To improve our predictive capacity-
potential exists for widespread immunotoxicity in humans and wildlife
species because of the worldwide lack of appropriate protective
standards. This is based on documented immune effects from high-level
exposure, plus a large amount of anecdotal data on humans and
wildlife, and strong experimental animal data.
exposure is widespread, it varies from region to region and individual
to individual. Based on anecdotal information, it is presumed
that exposure is greater in Eastern Europe and the former Soviet
Union and especially in developing coutnries because of lack of
adequate environmental regulations and enforcement.
lack of human epidemiological studies in the developing world
makes it impossible to determine the scale of immune modulation
and/or autoimmune disease among these populations. The consequences
of chemical exposure in developing countries may be severe because
of multiple confounders such as poverty, malnutrition and poor
medical care. The consequences will be difficult to identify because
of the lack of adequate control cohorts.
risk of exposure to known immunomodulators is sufficient to warrant
regulatory approaches that would limit exposure.
basic research is needed on the development of the immune system
of diverse animal species and the factors that drives it maturation
and senescence. Further study is needed to understand the mechanistic
role of synthetic chemicals in the alteration of these processes.
needs to be given to developing assays predictive of disease resistance
for a variety of species. It is important to know how immune modulation
affects increased prevalence of infectious diseases among humans
emphasis must be placed on developmental immunotoxicology. This
can be accomplished through collaborative research efforts to
standardize protocols, share specimens and to develop inexpensive,
rapid biomarkers of immunotoxicity. The use of the internet and
other online systems to apprise researchers of planned and ongoing
experiments will increase collaborative opportunities.
based on 'real world' situations (dose, duration of exposure,
timing) that include metabolism, pharmacokinetics, route of exposure
and target effects in a number of indicator species should be
developed for extrapolation to humans and other species.
criteria that include dose-response, time order (exposure precedes
effect), specificity, strength of association, coherence and predictability,
combined with laboratory validation, are needed to improve the
level of certainty in epidemiological studies.
epidemiological research among susceptible populations, especially
in developing countries, is needed.