Associating changes in the immune system with clinical diseases for interpretation in risk assessment.

Luster-MI; Germolec-DR; Parks-CG; Blanciforti-L; Kashon-M; Luebke-R

Current protocols in toxicology. Costa LG, Hodgson E, Reed DJ, Maines MD, Sassa S, Sipes IG, Bradfield C, Lawrence DA, Morgan KS, eds. New York: Wiley and Sons, Inc., 2004 Jan; 2(Suppl 20):18.1.1-18.1.20

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While it is well established that immunosuppression (see Terminology) can lead to an increased incidence and/or severity of infectious and neoplastic diseases, interpreting immunosuppression data from experimental immunotoxicology studies, or even epidemiological studies, for use in quantitative risk assessment is problematic. This is mostly due to a paucity of information on the health consequence of minimal-to-moderate immunosuppression, as might be expected to occur from inadvertent exposure to immunotoxic agents in humans. It is important that a scientifically sound framework be established that allows for the accurate quantitative interpretation of such data for use in the risk assessment process. In immunotoxicology, this may require, for example, development of a model to equate moderate changes in leukocyte counts. CD4 cell numbers, and/or immunoglobulin levels, tests which can be readily performed in human populations, to potential changes in the incidence or severity of infectious diseases, as well as establishing the social and economic impact of the incidence change. Although experimental animal models usually provide an opportunity to establish more reliable exposure estimates and conduct more informative immune tests than those that can be conducted in humans, extrapolating these findings across species is always of concern. The development of a framework to perform such extrapolations is currently being addressed by the authors' workgroup. As an integral process to this undertaking, a review of studies that address the qualitative and quantitative relationships between immune parameters and disease is contained herein. Initially, the most likely clinical consequences that may occur as a result of chronic mild-to-moderate immunosuppression are described as well as nonimmune factors that may modify these disease outcomes. Clinical and experimental animal studies that have examined immunosuppression disease relationships are reviewed and quantitative relationships when available are delineated to help address gaps in human health risk assessment. To address the potential social and economic consequences that could result from immunotoxicity, a brief description of the general impact of infectious disease is provided on these parameters. The most comprehensive data bases that address immunodeficiency disease relationships, specifically primary (genetic) immunodeficiency 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.

Diseases; Risk-analysis; Risk-factors; Immune-system; Infectious-diseases; Immunotoxins; Immunological-tests; Epidemiology; Quantitative-analysis; Models; Laboratory-animals; Animal-studies; Animals; Exposure-assessment; Immunoglobulins; Qualitative-analysis; Immune-system-disorders

20040101

Chapter

Costa-LG; Hodgson-E; Reed-DJ; Maines-MD; Sassa-S; Sipes-IG; Bradfield-C; Lawrence-DA; Morgan-KS

2004

HELD

Current protocols in toxicology

WV