Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment

Abstract

This overview is an update of the unit originally published in 2004. While the basic tenants of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process.

Immunotoxicology and Its Application in Risk Assessment

“…This approach is based on the assumption that a linear relationship exists between loss of immune responsiveness and increased risk of developing disease. A linear relationship is consistent with our understanding of immunological processes and is supported both by animal [17] and human studies [138] in which changes in immune tests correlated progressively with increased incidence of disease over a broad range.…”

“…In humans, mild-to-moderate suppression reduces efficacy of vaccines and increases the likelihood of common community-acquired infections, but does not affect the incidence of opportunistic infections that typically accompany severe forms of immunodeficiency diseases [10,11]. Maternal exposure to compounds such as polychlorinated biphenyls (PCBs) during the period of fetal immune system development may result in persistent immunosuppression in the offspring, at doses that do not affect adult immune function [1,12].…”

“…Likewise, identifying a small exposure-related change in infectious disease incidence is also difficult [16,17]. Researchers have linked low-to-moderate degrees of immunosuppression and increased infectious disease incidences with chronic psychological factors including separation and divorce, caregiving for Alzheimer's patients, and bereavement [11].…”