The somatostatin immunoregulatory circuit present at sites of chronic inflammation

Somatostatin is part of an immunoregulatory circuit that helps limit interf eron-gamma (IFN gamma) production at sites of chronic inflammation. In muri ne schistosomiasis, parasite eggs induce focal, chronic granulomatous infla mmation in the liver and intestines. These granulomas produce somatostatin 1-14 and express somatostatin receptor subtype number 2 (SSTR2), which is t he exclusive somatostatin receptor present in this inflammation. Granuloma and splenic macrophages as well as macrophage cell lines make somatostatin. There appears to be no other inflammatory cell source of the peptide. Vari ous inflammatory mediators induce this expression, whereas substance P inhi bits somatostatin production. Somatostatin can suppress IFN gamma secretion from T cells via interaction with the SSTR2 receptor expressed on these ce lls. Other cells within the granuloma also display SSTR2. The effect of som atostatin on these other cell types remains unknown. The thymus of normal m ice has a complete somatostatin regulatory circuit. The thymic epithelial a nd dendritic cells make somatostatin. Like the granulomas of murine schisto somiasis, the thymus expresses only SSTR2. Somatostatin likely has an impor tant role in thymic T cell education and selection.