Summary
Growth hormone, prolactin and somatostatin are polypeptide hormones of the neuroendocrine and peripheral nervous systems. In vitro, these have opposing effects on cells of the immune system. We compared the effects of these peptides on activation of neutrophils using a recombinant preparation of human growth hormone, human prolactin and octreotide, a long acting analog of somatostatin. In the absence of growth hormone, octreotide did not affect either neutrophil locomotion or respiratory burst. Octreotide, however, significantly antagonized growth hormone-induced activation of neutrophils for enhanced respiratory burst as well as growth hormone-induced inhibition of stimulated migration. As the effect of growth hormone on neutrophils is mediated by the prolactin receptor, its inhibition by octreotide was also tested using prolactin as priming agent. Data indicate comparable effects of octreotide on priming of neutrophils by prolactin. The effect of octreotide was dose-dependent and appeared to be selective, as activation of neutrophil respiration burst by γ-interferon, and inhibition of stimulated migration by tumor necrosis factor-α were unaffected by octreotide. The present study suggests that octreotide may act on neutrophils directly by antagonizing growth hormone or prolactin at the cellular level.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ader R, Felten D, Cohen N (1990) Interactions between the brain and the immune system. Ann Rev Pharmacol Toxicol 30:561–602
Adeyemi EO, Savage AP, Bloom SR, Hodgson HJF (1990) Somatostatin inhibits neutrophil elastase release in vitro. Peptides 11:869–871
Atkinson YH, Marasco WA, Lopez AF, Vadas MA (1988) Recombinant ] human tumor necrosis factor-alpha. Regulation of N-formylmethionyllcucylphenylalanine receptor affinity and function of human neutrophils. J Clin Invest 81:759–765
Bauer W, Briner U, Doepfner W (1982) SMS 201–995. A very potent and selective analogue octapeptide of somatostatin with prolonged action. Life Sci 31:1133–1141
Belcher HJCR, Ellis H (1990) Somatotropin and wound healing after injury. J Clin Endocrinol Metab 70:939–943
Bhathena SJ, Louie J, Schechter GP, Redman RS, Wahl L, Recant L (1981) Identification of human mononuclear leukocytes bearing receptors for somatostatin and glucagon. Diabetes 30:127–131
Comi RJ (1989) Pharmacology and use in pituitary tumors, pp 36–41. In: Gordon P, moderator. Somatostatin analogue (SMS 201–995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Int Med 110:35–50
Diamond RD, Lyman CA, Wysong DR (1991) Disparate effects of interferon-γ and tumor necrosis factor-α on early neutrophil respiratory burst and fungicidal responses to Candida albicans hyphae in vitro. J Clin Invest 87:711–720
Fehr J, Dahinden C (1979) Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. J Clin Invest 64:8–16
Fu Y-K, Arkins S, Wang BS, Kelley KW (1991) A novel role of growth hormone and insulin-like growth factor-I. Priming neutrophils for superoxide anion secretion. J Immunol 146:1602–1608
Fu YK, Arkins S, Fuh G, Cunningham BC, Wells JA, Fong S, Cronin MJ, Dantzer R, Kelley WK (1992) Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor. J Clin Invest 89:451–457
Gordon P, moderator (1989) Somatostatin analogue (SMS 201–995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Int Med 110:35–50
Harvath L, Robbins JD, Russell AA, Seamen KB (1991) CAMP and human neutrophil chemotaxis. Elevation of cAMP differentially affects chemotactic responsiveness. J Immunol 146:224–232
Kelley KW (1989) Growth hormone, lymphocytes and macrophages. Biochem Pharmacol 39:705–713
Kolasinski SL, Haines KA, Siegel EL, Cronstein BN, Abramson SB (1992) Neuropeptides and inflammation. A somatostatin analog as a selective antagonist of neutrophil activation by substance P. Arth Rheum 35:369–375
Mascardo RN, Sherline P (1982) Somatostatin inhibits rapid centrosomal separation and cell proliferation induced by epidermal growth factor. Endocrinology 111:1394–1396
Maton P (1989) Use in patients with gut neuroendocrine tumors, pp 41–44. In: Gordon P, moderator. Somatostatin analogue (SMS 201–995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Int Med 110:35–50
Maurer R, Caehwiler BH, Buescher HH, Hill RC (1982) Opiate antagonistic properties of octapeptide somatostatin analogue. Proc Natl Acad Sci USA 79:4815–4817
Pavelic K, Gabrilovac J, Bozikov V, Pavelic J, Petek M, Boranic M (1981) Somatostatin suppresses growth of murine myeloid leukemia in vivo. Blood 57:805–808
Pick E (1986) Microassays for superoxide and hydrogen peroxide production and nitroblue tetrazolium reduction using an enzyme immunoassay microplate reader. Methods Enzymol 132:407–421
Rivard N, Guan D, Turkelson CM, Petitclerc D, Solomon TE, Morisset J (1991) Negative control by Sandostatin on pancreatic and duodenal growth: a possible implication of insulin-like growth factor I. Reg. Peptides 34:13–23
Ruff MR, Wahl SM, Mergenhagen S, Pert CB (1985) Opiate receptor mediated chemotaxis of human monocytes. Neuropeptides 5:363–365
Sacerdote P, Bianchi M, Panerai AE (1990) Human monocyte chemotactic activity of calcitonin and somatostatin related peptides: Modulation by chronic peptide treatment. J Clin Endocrinol Metab 70:141–148
Schally AV (1988) Oncological applications of somatostatin analogues. Cancer Res 48:6977–6985
Schleifenbaum B, Moser R, Fehr J (1990) A defect in chemotaxis from interleukin-2. N Engl J Med 323:682–683
Serri O, Brazeau P, Kachra Z, Posner B (1992) Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action. Endocrinology 130:1816–1821
Snyderman R, Uhing RJ (1988) Phagocytic cells: Stimulus-response coupling mechanisms. In: Gallin et al (eds) Inflammation. Basic principles and clinical correlates. Raven Press, New York, pp 309–324
Stefano GB, Shipp MA, Scharrer B (1991) A possible immunoregulatory function for [Met]-enkephalin-Arg6-Phe7 involving human and invertebrate granulocytes. J Neuroimmunol 31:97–103
Steinbeck MJ, Roth JA (1989) Neutrophil activation by recombinant cytokines. Rev Infect Dis 11:549–568
Vruwink KG, Fletcher MP, Keen CL, Golub MS, Hendrickx AG, Gershwin ME (1991) Moderate zinc deficiency in rhesus monkeys. An intrinsic defect of neutrophil chemotaxis corrected by zinc repletion. J Immunol 146:244–249
Ward PA, Becker EL (1968) The deactivation of rabbit neutrophils by chemotactic factor and the nature of activatable esterases. J Exp Med 127:693–709
Wiedermann CJ (1987) Shared recognition molecules in the brain and lymphoid tissues: The polypeptide mediator network of psychoneuroimmunology. Immunol Lett 16:371–378
Wiedermann CJ, Niedermühlbichler M, Beimpold H, Braunsteiner H (1991a) Priming of normal human neutrophils by recombinant human growth hormone. Br J Haematol 78:19–22
Wiedermann CJ, Niedermühlbichler M, Beimpold H, Braunsteiner H (1991b) In vitro activation of neutrophils of the aged by recombinant human growth hormone. J Infect Dis 164:1017–1020
Wiedermann CJ, Niedermühlbichler M, Zilian U, Geissler D, Lindley I, Braunsteiner H (1991c) Priming of human neutrophils by tachykinins: Ttrftsin-like inhibition of in vitro chemotaxis stimulated by FMLP or interleukin-8. Reg Peptides 36:359–368
Wynick D, Bloom SR (1991) The use of the long-acting somatostatin analogue octreotide in the treatment of gut neuroendocrine tumors. J Clin Endocrinol Metab 73:1–3
Author information
Authors and Affiliations
Additional information
Thiis wo was supported by the Austrian Science Funds grant number P-7476-Med and the Austrian National Bank grant number 3954
Correspondence to C. J. Wiedermann at the above address
Rights and permissions
About this article
Cite this article
Wiedermann, C.J., Reinisch, N., Niedermühlbichler, M. et al. Inhibition of recombinant human growth hormone-induced and prolactin-induced activation of neutrophils by octreotide. Naunyn-Schmiedeberg's Arch Pharmacol 347, 336–341 (1993). https://doi.org/10.1007/BF00167454
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00167454