IL-1 is a major inflammatory cytokine that has diverse effects on different tissues. Despite the large number of publications on the effects of this cytokine very little is known about the physiological regulation of IL-1 gene expression and production. The objective of this project is to analyze these regulatory factors. Three models were used. 1. We previously identified and characterized a novel T-cell derived cytokine that induces IL-1 production. We are in the process of the cloning of the cDNA. 2. Macrophages in the lamina propria of the gut express IL-1 genes in normal mice. We analyzed the factors that regulate this IL-1 expression and found that environmental factors might be crucial in the induction of IL-1 genes in the gut macrophages. 3. Several observations suggest that IL-1 has effects on the CNS. However, we did not find IL-1 mRNA in the normal brain by a sensitive PCR analysis. Intracerebral injection of LPS dramatically increased IL-1 gene expression in the brain within 3 hrs. These observations suggest that IL-1 has a role in adapting both the CNS and the immune system to the state of inflammation and immune response.