GRANULOMAS IN MURINE SCHISTOSOMIASIS-MANSONI HAVE A SOMATOSTATIN IMMUNOREGULATORY CIRCUIT

The role of somatostatin (SRIF) in controlling the granulomatous infla mmatory response to infection with the parasite Schistosoma mansoni wa s explored in mice. The murine granulomas contain SRIF-14. Immunoreact ive SRIF and preproSRIF localize in the cytoplasmic granules of macrop hases within the granulomas. The granulomas contain mRNA for preproSRI F and are not innervated. The production of SRIF by the inflammatory c ells appears to be inducible. The granulomas contain mRNA for the SRIF receptors sst(2)A and sst(2)B, which are expressed mainly on CD4(+) T lymphocytes and bind SRIF-14 with high affinity. Antigens from the sc histosome eggs stimulate granuloma T lymphocytes to produce cytokines. Interferon-gamma (IFN-gamma) is one such cytokine made by CD4(+) T ly mphocytes. SRIF-14 suppresses antigen-induced IFN-gamma production fro m granuloma cells, and this effect is blocked by anti-sst(2) antibody. SRIF was shown to inhibit IFN-gamma-induced immunoglobulin G2a (IgG2a ) synthesis in murine schistosomiasis. SRIF also blocks substance P (S P)-stimulated IFN-gamma and IgG2a secretion. Schistosome-infected anim als treated with the SRIF analog octreotide form smaller granulomas th at secrete substantially less IFN-gamma I and IgG2a. Unpublished obser vations suggest that SRIF does not modulate schistosome egg antigen- o r concanavalin A-stimulated granuloma lymphocyte proliferation in muri ne schistosomiasis. In conclusion, SRIF may be an important factor in the control of the granulomatous inflammatory response in murine schis tosomiasis. Copyright (C) 1996 by W.B. Saunders Company