This laboratory is involved in studies to describe the role of mononuclear cells in the inflammatory process and in various disease states. Experiments have been designed to study cytokine gene expression in normal and viral (HTLV-III) - infected human monocytes. Previous studies have demonstrated that monocytes from patients suffering from acquired immunodeficiency syndrome (AIDS) are defective in their ability to produce interleukin 1 (IL-1), a cytokine responsible for activating T lymphocytes. Our experiments indicate that the IL-1 gene is transcribed in lipopolysaccharide-stimulated monocytes from AIDS patients; the level of transcription varies between patients as compared to normal controls. In a few patients, high levels of IL-1 mRNA are detectable in unstimulated monocytes, indicating a spontaneous production of IL-1 message. In situ hybridization techniques are being used to expand these findings. Further studies will address post-transcriptional events which could account for the decreased IL-1 protein activity in AIDS monocytes. The functional role of the IL-2 receptor on the cell surface of activated monocytes is being assessed. Preliminary evidence suggests that IL-2 inhibits transcription of the IL-1Beta gene in activated monocytes. Whether this inhibition acts through the IL-2 receptor remains to be proven.
