Abstracts of the International Life Sciences Institute. Application of Flow Cytometry to Immunotoxicity Testing, Summary of a Workshop, October 9-10, 1997. Washington DC: International Life Sciences Institute, 1999 Oct; :5-6
Dr. Raymond E. Biagini, Centers for Disease Control and Prevention, Cincinnati, OH, examined the immunotoxicity of lead. He observed that the effects of lead on the immune systems of animals include changes in antibody synthesis, macrophage activity, lymphoproliferative responses, and autoimmune responses (McCabe 1994, McCabe and Lawrence 1994, Zelikoff and Cohen 1996). Such studies often yield conflicting results reflecting, at least in part, interlaboratory variability in study design, sampling, and analysis. He concluded that the most consistent, reproducible effect was decreased host resistance to bacterial, viral, and parasitic challenges. There have been few studies using flow cytometry to determine the effects of lead on lymphoid cell phenotypes other than in the context of examining potential mechanisms of toxicity. For example, lead-associated changes in cell-mediated immunity were correlated with differential effects on CD4+ T cell subsets in the spleen, whereas the lead-induced increase in IgM production was associated with enhanced splenic B cell Ia molecule expression and differentiation (McCabe and Lawrence 1990, 1991). The mechanistic studies in animals generally relied on cell sources that are not amenable to sampling in humans (e.g., spleen or lymph nodes). Dr. Biagini concluded that data from the animal studies are not directly comparable with the results of human studies, where immunophenotyping is performed on peripheral blood mononuclear cells from workers exposed to lead in the workplace (Pinkerton et al. 1998). Comparisons between animals and humans are constrained because peripheral blood typically has not been used for immunophenotyping studies in animals. Dr. Biagini reviewed recent epidemiologic studies in lead-exposed workers in which their immunophenotypic profiles were examined (Cohen et al. 1989, Fischbein et al. 1993, Ündeer et al. 1996, Sata et al. 1997). These studies exclusively used peripheral blood and yielded inconsistent results. Depending on the study, exposure to lead resulted in increases, decreases, or no change in the absolute numbers and/or percentages of cells expressing CD3, CD4, CD8, CD16, CD19, CD56, and other surface markers. Although there is little evidence that the results of animal studies correspond to observed human responses to lead exposure, the animal findings are aiding in the design of epidemiologic studies. For example, the observation of consistent changes in host resistance in lead-exposed animals (Lawrence 1981, Kowolenko et al. 1991) has prompted the revision of questionnaires used in epidemiologic studies to include questions about recent illness and infections. However, the limitations of cohort size (usually <200 people) makes it difficult to detect statistical differences in nonspecific illness and infection prevalence.
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Abstracts of the International Life Sciences Institute. Application of Flow Cytometry to Immunotoxicity Testing, Summary of a Workshop, October 9-10, 1997