Abstract
Background: Somatostatin plays an important role in the communication between the nervous, endocrine, and immune systems. Although somatostatin or its analogues have been shown to modulate a number of immune functions, their immunomodulatory effects are not uniform and are strongly dependent on the underlying cell system. Aim: The aim of our study was to analyze the immunomodulatory effects of somatostatin and its analogue octreotide on peripheral blood mononuclear cells (PBMC) in vitro. Materials/subjects: We used lipopolysaccharide-activated cells from normal glucose tolerant (NGT) subjects and from Type 2 diabetes mellitus (T2DM) patients as T2DM is associated with chronic, low-grade inflammation, and measured immune mediator release with multiplex bead-based assays. Results: Our data showed no statistically significant effects on the secretion of the cytokines interleukin (IL)-1β, IL-6, IL-10, IL-12, interferon-γ and tumor necrosis factor-α as well as the chemokines IL-8 and monocyte chemoattractant protein (MCP)-1, either on PBMC from T2DM patients or on those from NGT controls. However, a trend towards a dose-dependent biphasic effect was observed for IL-6, IL-10 and MCP-1 with reduced immune mediator levels at low and increased/unaltered levels at higher somatostatin or octreotide concentrations. These observations could not be explained by interference with cell viability or proliferation. Conclusions: We could not confirm immunomodulatory properties of somatostatin and octreotide on PBMC. Further analyses are necessary to explain the interaction between neuropeptides and the immune system.
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Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med 1996, 334: 246–54.
ten Bokum AM, Hofland LJ, van Hagen PM. Somatostatin and somatostatin receptors in the immune system: a review. Eur Cytokine Netw 2000, 11: 161–76.
Ryu SY, Jeong KS, Yoon WK, et al. Somatostatin and substance P induced in vivo by lipopolysaccharide and in peritoneal macrophages stimulated with lipopolysaccharide or interferon-gamma have differential effects on murine cytokine production. Neuroimmunomodulation 2000, 8: 25–30.
Lattuada D, Casnici C, Crotta K, et al. Inhibitory effect of pasireotide and octreotide on lymphocyte activation. J Neuroimmunol 2007, 182: 153–9.
Hernanz A, Tato E, De la Fuente M, de Miguel E, Arnalich F. Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha production by whole blood cells from healthy young and old subjects. J Neuroimmunol 1996, 71: 25–30.
Komorowski J, Stepien H. Somatostatin (SRIF) stimulates the release of interleukin-6 (IL-6) from human peripheral blood monocytes (PBM) in vitro. Neuropeptides 1995, 29: 77–81.
Kolb H, Mandrup-Poulsen T. An immune origin of type 2 diabetes? Diabetologia 2005, 48: 1038–50.
Müller S, Martin S, Koenig W, et al. Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia 2002, 45: 805–12.
Herder C, Baumert J, Thorand B, et al. Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002. Diabetologia 2006, 49: 921–9.
Herder C, Kolb H, Koenig W, et al. Association of systemic concentrations of macrophage migration inhibitory factor with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg, Survey 4 (KORA S4). Diabetes Care 2006, 29: 368–71.
Herder C, Klopp N, Baumert J, et al. Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case-Cohort Study, 1984–2002. Diabetologia 2008, 51: 276–84.
Rose B, Herder C, Löffler H, Kolb H, Martin S. Combined activation of innate and T cell immunity for recognizing immunomodulatory properties of therapeutic agents. J Leukoc Biol 2004, 75: 624–30.
Herder C, Schneitler S, Rathmann W, et al. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab 2007, 92: 4569–74.
Blum AM, Metwali A, Mathew RC, et al. Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. J Immunol 1992, 149: 3621–6.
Taylor AW, Yee DG. Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 2003, 44: 2644–9.
Casnici C, Lattuada D, Crotta K, et al. Effects of chimeric somatostatin-dopamine molecules on human peripheral blood lymphocytes activation. J Neuroimmunol 2006, 179: 9–17.
Muscettola M, Grasso G. Somatostatin and vasoactive intestinal peptide reduce interferon gamma production by human peripheral blood mononuclear cells. Immunobiology 1990, 180: 419–30.
Peluso G, Petillo O, Melone MA, et al. Modulation of cytokine production in activated human monocytes by somatostatin. Neuropeptides 1996, 30: 443–51.
Yousefi S, Vaziri N, Carandang G, et al. The paradoxical effects of somatostatin on the bioactivity and production of cytotoxins derived from human peripheral blood mononuclear cells. Br J Cancer 1991, 64: 243–6.
Tang WF, Wang YG, Zhu L, et al. Effect of somatostatin on immune inflammatory response in patients with severe acute pancreatitis. J Dig Dis 2007, 8: 96–102.
Herberth G, Daegelmann C, Weber A, et al; LISAplus Study Group. Association of neuropeptides with Th1/Th2 balance and allergic sensitization in children. Clin Exp Allergy 2006, 36: 1408–16.
Agro A, Stanisz AM. Neuroimmunomodulation: classical and non-classical cellular activation. Adv Neuroimmunol 1995, 5: 311–9.
Elliott DE, Metwali A, Blum AM, Sandor M, Lynch R, Weinstock JV. T lymphocytes isolated from the hepatic granulomas of schisto-some-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA. J Immunol 1994, 153: 1180–6.
Elliott DE, Li J, Blum AM, et al. SSTR2A is the dominant somatostatin receptor subtype expressed by inflammatory cells, is widely expressed and directly regulates T cell IFN-gamma release. Eur J Immunol 1999, 29: 2454–63.
Shimon I, Yan X, Taylor JE, Weiss MH, Culler MD, Melmed S. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. J Clin Invest 1997, 100: 2386–92.
Schmid HA, Schoeffter P. Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors. Neuroendocrinology 2004, 80(Suppl 1): 47–50.
Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999, 20: 157–98.
ter Veld F, Herder C, Mussmann R, Martin S, Kempf K. Somatostatin receptor expression in peripheral blood of type 2 diabetes mellitus patients. Horm Metab Res 2007, 39: 230–2.
Yan S, Li M, Chai H, et al. TNF-alpha decreases expression of somatostatin, somatostatin receptors, and cortistatin in human coronary endothelial cells. J Surg Res 2005, 123: 294–301.
Cipolletta C, Ryan KE, Hanna EV, Trimble ER. Activation of peripheral blood CD14+ monocytes occurs in diabetes. Diabetes 2005, 54: 2779–86.
Fogelstrand L, Hulthe J, Hultén LM, Wiklund O, Fagerberg B. Monocytic expression of CD14 and CD18, circulating adhesion molecules and inflammatory markers in women with diabetes mellitus and impaired glucose tolerance. Diabetologia 2004, 47: 1948–52.
Herder C, Haastert B, Muller-Scholze S, et al. Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes 2005, 54(Suppl 2): S11–7.
Herder C, Hauner H, Haastert B, et al. Hypoadiponectinemia and proinflammatory state: two sides of the same coin?: results from the Cooperative Health Research in the Region of Augsburg Survey 4 (KORA S4). Diabetes Care 2006, 29: 1626–31.
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ter Veld, F., Rose, B., Mussmann, R. et al. Effects of somatostatin and octreotide on cytokine and chemokine production by lipopolysaccharide-activated peripheral blood mononuclear cells. J Endocrinol Invest 32, 123–129 (2009). https://doi.org/10.1007/BF03345700
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DOI: https://doi.org/10.1007/BF03345700