[PDF][PDF] Linking environmental agents and autoimmune diseases.
GS Cooper, D Germolec, J Heindel… - Environmental Health …, 1999 - ehp.niehs.nih.gov
GS Cooper, D Germolec, J Heindel, M Selgrade
Environmental Health Perspectives, 1999•ehp.niehs.nih.govThis monograph is based on the workshop" Linking Environmental Agents and Autoimmune
Diseases" held at the National Institute of Environmental Health Sciences held 1-3
September 1998. The workshop brought together immunologists, clinicians,
epidemiologists, molecular biologists, and toxicologists to review current knowledge about
environmental links to autoimmune disease and to identify data gaps and future research
needs.(Environmental agents were defined as xenobiotic chemicals in the environment; …
Diseases" held at the National Institute of Environmental Health Sciences held 1-3
September 1998. The workshop brought together immunologists, clinicians,
epidemiologists, molecular biologists, and toxicologists to review current knowledge about
environmental links to autoimmune disease and to identify data gaps and future research
needs.(Environmental agents were defined as xenobiotic chemicals in the environment; …
This monograph is based on the workshop" Linking Environmental Agents and Autoimmune Diseases" held at the National Institute of Environmental Health Sciences held 1-3 September 1998. The workshop brought together immunologists, clinicians, epidemiologists, molecular biologists, and toxicologists to review current knowledge about environmental links to autoimmune disease and to identify data gaps and future research needs.(Environmental agents were defined as xenobiotic chemicals in the environment; viruses and infec-tious agents were not considered in thisparticular workshop.) The impetus for the workshop was the question of whether environmental agents affect the development or progression of autoimmune disease. If so, the ultimate goal is to understand the role of environmental agents and the underlying mechanisms through which these agents act so that the potential risks of exposure to these agents can be assessed and reduced. The workshop's objectives were to assem-ble experts from a variety of fields and provide a forum where they could interact; review what is known about links between environmen-tal exposures and autoimmune disease; identify and prioritize research needs; and develop an integrated, multidisciplinary research agenda. The following critical questions framed the workshop's program: a) Is there an increased risk for autoimmune disease as a resultof environmental exposures? If so, what is the magnitude of that risk? Most autoimmune diseases are relatively rare and hence risk may appear to be low when based on a specific disease. The risk would be greater if several autoimmune diseases were affected by a chemical exposure, possibly via common mechanisms. For the population at large, the risk is probably smaller than it is for certain sensitive popu-lations. For any individual chemical the risk may be small, but if a number of (possibly structurally similar) chemicals have similar effects, the magnitude of risk increases. Finally, the dose response, prevalence, and persistence of the chemical (s) in question all affect the magnitude of risk. Information with respect to these issues is needed to understand the importance of environmental agents in the devel-opment or expression of autoimmune disease. b) What are the underlying mechanisms? Because many autoimmune diseases involve different organ systems, pathogenesis is likely to involve multiple mechanisms. There are several potential targets for chemicals, including the immune system, the affected organ (s)(particularly with respect to alteration of antigenic expression), and the neuroendocrine system. If common mechanisms can be identified, it may be possible to group certain diseases or chemi-cals together. Understanding the underlying mechanisms (s) also is crit-ical for developing biomarkers of effect that can be used in testing strategies. It would also be useful to know whether there are common mechanisms across the varied forms of immune response (immune suppression, allergy, and autoimmune disease). Finally, mechanistic data would help determine structure-activity relationships, which frequently are thefirst consideration in hazardidentification. c) How should we evaluate the role of environmental agents using animal testing methods? Chemicals that suppress immune responses may enhancesusceptibility to infectious and neoplastic disease, and inappropriate stimulation of the immune system may result in allergic or autoimmune disease. To date, toxicologists have primarily focused their research on immune suppression and allergy. So much progress has been made in the area of immune suppression that the US Environmental …
ehp.niehs.nih.gov