The somatostatin immunoregulatory circuit present at sites of chronic inflammation

Abstract

Somatostatin is part of an immunoregulatory circuit that helps limit interferon-g (IFNg) production at sites of chronic in¯ammation. In murine schistosomiasis, parasite eggs induce focal, chronic granulomatous in¯ammation in the liver and intestines. These granulomas produce somatostatin 1±14 and express somatostatin receptor subtype number 2 (SSTR 2 ), which is the exclusive somatostatin receptor present in this in¯ammation. Granuloma and splenic macrophages as well as macrophage cell lines make somatostatin. There appears to be no other in¯ammatory cell source of the peptide. Various in¯ammatory mediators induce this expression, whereas substance P inhibits somatostatin production. Somatostatin can suppress IFNg secretion from T cells via interaction with the SSTR 2 receptor expressed on these cells. Other cells within the granuloma also display SSTR 2 . The effect of somatostatin on these other cell types remains unknown. The thymus of normal mice has a complete somatostatin regulatory circuit. The thymic epithelial and dendritic cells make somatostatin. Like the granulomas of murine schistosomiasis, the thymus expresses only SSTR 2 . Somatostatin likely has an important role in thymic T cell education and selection.

Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages

“…Cells of the monocyte lineage, i.e., macrophages, are known to be important components of the human immune circuitry and are involved in the modulation of immunological and inflammatory responses. Although the inhibitory role of SRIF-14 in cells of the monocyte lineage has been studied extensively in rodents [7][8][9][10][11][12][13][14], little is known about whether these findings can be extended to human monocytes. In this article, we report for the first time the expression and functional effects of distinct SRIF receptors in human macrophages differentiated from PBMC-derived monocytes.…”

The role of cortistatin in the human immune system

“…Murine granuloma CD4+ T lymphocytes express sst 2 (in contrast to human lymphocytes). Both SRIF and octreotide markedly A c c e p t e d M a n u s c r i p t reduce the production of IFN- by granuloma T lymphocytes resulting in a decreased granuloma response (Elliott and Weinstock, 1996;Elliott et al, 1999;Weinstock and Elliott, 2000).…”

Somatostatin receptor subtypes in human immune cells

“…The widely used synthetic analogue, octreotide, binds with high affinity only to sst subtypes 2 and 5 and with lower affinity to receptor subtype 3; binding to receptor subtypes 1 and 4 is undetectable (8,9). sst have been demonstrated in both rodent and human immune cells (10,11). In this paper, some of the recent novel insights in the expression and functional significance of ssts in human immune cells are discussed.…”