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The Substance P and Somatostatin Interferon-γ Immunoregulatory Circuita

Authors

  • JOEL V. WEINSTOCK,

    Corresponding author
    1. Division of Gastroenterology-Hepatology, Department of Medicine, University of Iowa, lowa City, Iowa 522423 USA
      Address for correspondence: Joel V. Weinstock or David Elliott, Gastroenterology-Hepatology Division, Department of Internal Medicine, 4607JCP, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
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  • DAVID ELLIOTT

    Corresponding author
    1. Division of Gastroenterology-Hepatology, Department of Medicine, University of Iowa, lowa City, Iowa 522423 USA
      Address for correspondence: Joel V. Weinstock or David Elliott, Gastroenterology-Hepatology Division, Department of Internal Medicine, 4607JCP, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
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  • a

    Grants from the National Institutes of Health (DK38327, DK07663, DK25295), the Crohn's and Colitis Foundation of America, Inc., and the Veterans Administration supported this research. SEA was supplied by the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases.

Address for correspondence: Joel V. Weinstock or David Elliott, Gastroenterology-Hepatology Division, Department of Internal Medicine, 4607JCP, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.

Abstract

Abstract: Murine schistosomiasis mansoni is a parasitic disease in which flukes living in the portal vein of the host produce ova that deposit in the liver and intestines. In these organs, ova release antigens that induce chronic, focal granulomatous inflammation. IFN-γ is an inflammatory cytokine important in macrophage activation and B-cell differentiation. A substance P (SP)/somatostatin (SOM) neurokine immunoregulatory circuit controls IFN-γ production in schistosome granulomas. SP stimulates, while SOM inhibits IFN-γ release, modulating IFN-γ-dependent circuitry. SP and SOM function through interaction with authentic SP and SOM receptors located on granuloma T cells. Also, the granulomas produce authentic SP and SOM14, as evidenced by the presence of mRNA and product. The granulomas have no nerves. This and other data suggest that the inflammatory cells make these neurokines. Granuloma macrophages produce SOM. Macrophages from various sources express SOM mRNA in response to LPS, IFN-γ, IL-10 or several other inflammatory mediators. Thus, the inflammation of murine schistosomiasis has a complete SP/SOM immunoregulatory circuit, which in turn is subject to immunoregulation.

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