The Immunotoxicology Group studies the adverse effects on the immune system resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and biological materials. The ongoing objectives include efforts: (1) to evaluate and examine the influence of selected drugs or environmental chemicals on the immune response and relate alterations in immunological functions with general and specific organ toxicity; (2) when applicable, to examine potential mechanism of action; (3) to relate changes in immunological functions with altered host resistance following challenge with tumor cells or infectious agents; and (4) to refine and validate a panel of immune and host resistance procedures in order to better define immunotoxicity and correlate changes in immune function with altered host resistance. Studies were performed in the following areas: (a) Development and utilization of B cell maturation as an in vitro model to sequentially examine the cellular and molecular events associated with chemical-induced immunotoxicity. General methodology includes the use of flow cytometry as well as methods for examining second messenger, cellular proliferation, and cellular differentiation. Chemicals and drugs that have been examined include compounds that modulate arachidonic acid products, tetrachlorodibenzo-p-dioxin, polycyclics, pertussis toxin, and methotrexate. (b) Development of model systems which allow assessment of neutrophil and alveolar macrophage function, maturation potential, and ability to respond to physiological activation. Endpoints for these assays include production of soluble mediators, surface markers, and effector cell function. (c) Evaluation and examination of immunotoxicity associated with the tumorigenic process in mice neonatally administered a liver promotor (diethylnitrosamine), in mice exposed to a contaminated drinking water sample, and in mice exposed to antinucleosides used in the treatment of AIDS (i.e., AZT, DDC, and DDA) or other AIDS therapeutics (e.g., alpha-interferon, AL721).
