Investigative Immunotoxicology. Tryphonas H, Fournier M, Blakley BR, Smits JE, Brousseau-P, eds., Boca Raton, FL: CRC Press, Inc., 2005 Jan; :165-181
Although immunosuppression can lead to an increased incidence and severity of infectious and neoplastic diseases, interpreting data from experimental immunotoxicology studies, or even epidemiologic studies, for quantitative risk assessment purposes has been problematic. This is particularly true when the immunological effects, as may be expected from inadvertent exposures in human populations, are slight in nature. In order to accurately predict the risk of immunotoxic exposures in human populations, a scientifically sound framework needs to be established that will allow for the accurate and quantitative interpretation of experimental or clinical immune test data to human health effects. This may require, for example, development of models to equate moderate changes in the numbers of circulating lymphocyte populations or serum immunoglobin levels, tests that can readily be performed in humans, to potential changes in the incidence or severity of infectious diseases. As an integral step in the development of such a framework, studies on the qualitative and quantitative relationships between immune parameters and disease are reviewed. Initially, the most likely clinical consequences that may occur from chronic mild to moderate immunosuppression are described as well as physiological factors and study design issues that may modify these disease outcomes. Clinical and experimental animal studies that address relationships between immune function and disease development are also discussed in detail and quantitative relationships are described. The most comprehensive databases that address immunodeficiency disease relationships, specifically primary immunodeficiency diseases and AIDS, are not discussed, as these represent extreme examples of immunosuppression, and neither the specific clinical diseases that result nor the eventual outcomes have much in common to that which occurs in individuals With chronic mild to moderate immunosuppression. It is useful to provide clarification of certain terminology. "Immunosuppression," "immunodeficiency," and "immunocompromised" are nonquantitative terms that reflect a reduced capacity of the immune system to respond to antigens, and are often used interchangeably in immunotoxicology. For the purpose of risk assessment, immunosuppression can be defined as a loss in the ability of the immune system to respond to a challenge at a level that is considered normal, regardless of whether clinical disease ensues. Immunodeficiency often represents an alteration in the immune system that can potentially lead to clinical disease, whether primary (i.e., genetic etiology) or secondary (epigenetic) in nature. The term immunocompromised, like immunosuppression, indicates a deficient immune response, independent of whether it is maladaptive. Immunotoxicity encompasses each of these terms, but specifies that the effect on the immune system originates from xenobiotic exposure.