Granulomas in murine schistosomiasis mansoni have a somatostatin immunoregulatory circuit

The role of somatostatin (SRIF) in controlling the granulomatous inflammatory response to infection with the parasite Schistosoma mansoni was explored in mice. The murine granulomas contain SRIF-14. Immunoreactive SRIF and prepro SRIF localize in the cytoplasmic granules of macrophages within the granulomas. The granulomas contain mRNA for prepro SRIF and are not innervated. The production of SRIF by the inflammatory cells appears to be inducible. The granulomas contain mRNA for the SRIF receptors sst2A and sst2B, which are expressed mainly on CD4- T lymphocytes and bind SRIF-14 with high affinity. Antigens from the schistosome eggs stimulate granuloma T lymphocytes to produce cytokines. Interferon-gamma (IFN-gamma) is one such cytokine made by CD4+ T lymphocytes. SRIF-14 suppresses antigen-induced IFN-gamma production from granuloma cells, and this effect is blocked by anti-sst2 antibody. SRIF was shown to inhibit IFN-gamma-induced immunoglobulin G2a (lgG2a) synthesis in murine schistosomiasis. SRIF also blocks substance P (SP)-stimulated IFN-gamma and lgG2a secretion. Schistosome-infected animals treated with the SRIF analog octreotide form smaller granulomas that secrete substantially less IFN-gamma and lgG2a. Unpublished observations suggest that SRIF does not modulate schistosome egg antigen- or concanavalin A-stimulated granuloma lymphocyte proliferation in murine schistosomiasis. In conclusion, SRIF may be an important factor in the control of the granulomatous inflammatory response in murine schistosomiasis.