The Immunotoxicology Group is continuing the assessment of immunotoxicity of AIDS therapeutics. The ongoing objectives include: (1) to evaluate the potential adverse effects of promising AIDS therapeutics on systemic as well as local systems and to examine potential mechanisms of toxicity (or therapeutic action, if unknown); (2) to relate these observed changes in immune function to changes in host resistance in order to improve risk assessment. Studies were performed in the following areas: a) studies on pentamidine isethionate and related analogs on lung macrophages. The endpoints for these studies focus on cytokine production: b) development of animal models, particularly the SCID-human reconstituted mice, to better study potential immunotoxicity of AIDS therapeutics; and c) development of mathematical models to better establish the quantitative relationship of altered immune function tests to clinical disease. The results of these studies demonstrated that the following endotoxin administration, pentamidine has a protective and anti-inflammatory role both systemically and in the lung and suggets that inhibition of inflammatory cytokines such as TNF and IL-6 may be one mechanism operable in the therapeutic activity of the drug against P. carinii pneumonia.
