Effects of octreotide on jejunal hypersensitivity triggered by Cryptosporidium parvum intestinal infection in an immunocompetent suckling rat model
J. Bai
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Department of Pharmacology, Xinjiang Medical University, Urumqi, Xinjiang, China
Search for more papers by this authorS. Khaldi
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorG. Gargala
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorA. Baishanbo
Department of Pharmacology, Xinjiang Medical University, Urumqi, Xinjiang, China
Search for more papers by this authorA. François
Department of Histopathology, Rouen University Hospital and University of Rouen, Rouen, France
Search for more papers by this authorJ. J. Ballet
Department of Immunology, Caen University Hospital and University of Caen, Caen, France
Search for more papers by this authorP. Ducrotté
Gastroenterology Unit, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorJ. Fioramonti
Neurogastroenterology and Nutrition Unit, INRA, Toulouse, France
Search for more papers by this authorL. Favennec
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorL. Le Goff
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorJ. Bai
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Department of Pharmacology, Xinjiang Medical University, Urumqi, Xinjiang, China
Search for more papers by this authorS. Khaldi
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorG. Gargala
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorA. Baishanbo
Department of Pharmacology, Xinjiang Medical University, Urumqi, Xinjiang, China
Search for more papers by this authorA. François
Department of Histopathology, Rouen University Hospital and University of Rouen, Rouen, France
Search for more papers by this authorJ. J. Ballet
Department of Immunology, Caen University Hospital and University of Caen, Caen, France
Search for more papers by this authorP. Ducrotté
Gastroenterology Unit, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorJ. Fioramonti
Neurogastroenterology and Nutrition Unit, INRA, Toulouse, France
Search for more papers by this authorL. Favennec
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorL. Le Goff
Parasitology Department, Rouen University Hospital and Institute for Biomedical Research, University of Rouen, Rouen, France
Search for more papers by this authorAbstract
Background Similar to other bacterial or protozoan infections, human cryptosporidiosis may trigger postinfectious irritable bowel syndrome (IBS)-like symptoms, a condition in which enhanced visceral perception of pain during intestinal distension plays a pivotal role. In an immunocompetent suckling rat model which mimicks features of postinfectious IBS, Cryptosporidium parvum infection induces long-lasting jejunal hypersensitivity to distension in association with intestinal activated mast cell accumulation. The aim of the present study was to explore in this model whether octreotide, a somatostatin agonist analog, could prevent the development of jejunal hypersensitivity and intestinal mast cell/nerve fiber accumulation.
Methods Five-day-old Sprague–Dawley rats were infected with C. parvum and treated 10 days later with octreotide (50 g kg−1day−1, i.p.) for 7 days.
Key Results Compared with untreated infected rats, octreotide treatment of infected rats resulted in increased weight gain [day 23 postinfection (PI)], decreased food intake (day 16 PI), and a reduction in jejunal villus alterations (day 14 PI), CD3+IEL (day 37 PI) and mast cell (days 37 and 50 PI) accumulations, nerve fiber densities (day 50 PI), and hypersensitivity to distension (day 120 PI). In uninfected rats, the effects of octreotide treatment were limited to higher weight gain (days 16 and 23 PI) and decreased food intake (day 23 PI) compared with uninfected-untreated rats.
Conclusions & Inferences Data confirms the relevance of the present rat model to postinfectious IBS studies and prompt further investigation of somatostatin-dependent regulatory interactions in cryptosporidiosis.
References
- 1 Azpiroz F, Bouin M, Camilleri M et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Motil 2007; 19: 62–88.
- 2 Barbara G, Wang B, Stanghellini V et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology 2007; 132: 26–37.
- 3 Barbara G, Stanghellini V, De Giorgio R et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004; 126: 693–702.
- 4 Bueno L, de Ponti F, Fried M et al. Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity. Neurogastroenterol 2007; 19: 89–119.
- 5 Miller HR, Huntley JF, Newlands GF, Irvine J. Granule chymases and the characterization of mast cell phenotype and function in rat and mouse. Monogr Allergy 1990; 27: 1–30.
- 6 Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut 2004; 53: 1096–101.
- 7 Morgan UM, Xiao L, Fayer R, Lal AA, Thompson RC. Epidemiology and strain variation of Cryptosporidium parvum. Contrib Microbiol 2000; 6: 116–39.
- 8 Thielman NM, Guerrant RI. Clinical practice: acute infectious diarrhea. N Engl J Med 2004; 350: 38–47.
- 9 Hunter PR, Hughes S, Woodhouse S et al. Health sequelae of human cryptosporidiosis in immunocompetent patients. Clin Infect Dis 2004; 39: 504–10.
- 10 DuPont AW. Postinfectious irritable bowel syndrome. Clin Infect Dis 2008; 46: 594–9.
- 11 Gwee KA. Postinfectious irritable bowel syndrome. Curr Treat Options Gastroenterol 2001; 4: 287–91.
- 12 Hortwitz BJ, Fisher RS. The irritable bowel syndrome. N Engl J Med 2001; 344: 1846–50.
- 13 Spiller R, Campbell E. Postinfectious irritable bowel syndrome. Curr Opin Gastroenterol 2006; 22: 13–7.
- 14 Marquet P, Saubamea B, Snouber-Choucha L, Gafa V, Kapel N, Barbot-Trystram L. Evidence for intestinal heterogenic expression of di-tripeptides transporter PepT1 during experimental cryptosporidiosis in neonatal rats. Parasitol Res 2008; 104: 985–91.
- 15 Novak SM, Sterling CR. Susceptibility dynamics in neonatal BALB/c mice infected with Cryptosporidium parvum. J Protozool 1991; 38: 103S–4S.
- 16 Serna H, Porras M, Vergara P. Mast cell stbilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast cell hyperplasia and intestinal dysmobility in experimental Trichinella spiralis inflammation in the rat. J Pharmacol Exp Ther 2006; 319: 1104–11.
- 17 Suzuki T, Sasaki T, Takagi H, Sato K, Ueda K. The effectors responsible for gastrointestinal nematode parasites, trichinella spiralis, expulsion in rats. Parasitol Res 2008; 103: 1289–95.
- 18 Van Op den bosch J, Adriaensen D, Van Nassauw L, Timmermans JP. The role(s) of somatostatin, structurally related peptides and somatostatin receptors in the gastrointestinal tract: a review. Regul Pept 2009; 156: 1–8.
- 19 Pinter E, Helyes Z, Szolcsanyi J. Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Therapeut 2006; 112: 440–56.
- 20 Barnett P. Somatostatin and somatostatin receptor physiology. Endocrine 2003; 20: 255–64.
- 21 Carlton SM, Du J, Davidson E, Zhou S, Coggeshall RE. Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors. Pain 2001; 90: 233–44.
- 22 Ferone D, Boschetti M, Resmini E et al. Neuroendocrine-immune interactions: the role of cortistatin/somatostatin system. Ann N Y Acad Sci 2006; 1069: 129–44.
- 23 Guillermet-Guibert J, Lahlou H, Cordelier P, Bousquet C, Pyronnet S, Susini C. Physiology of somatostatin receptors. J Endocrinol Invest 2005; 28: 5–9.
- 24 Binimelis J, Webb SM, Monés J. Somatostatin and irritable bowel syndrome. Lancet 1987; 2: 1533.
- 25 Hasler WL, Soudah HC, Owyang C. A somatostatin analogue inhibits afferent pathways mediating perception of rectal distension. Gastroenterology 1993; 104: 1390–7.
- 26 Hasler WL, Soulah HC, Owyang C. Somatostatin analog inhibits afferent response to rectal distension in diarrhea-predominant irritable bowel patients. J Pharmacol Exp Ther 1994; 268: 1206–11.
- 27 Schwetz I, Naliboff B, Munakata J et al. Anti-hyperalgesic effect of octreotide in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2004; 19: 123–31.
- 28 Talley NJ, Turner L, Middleton WR. Somatostatin and symtomatic relief of irritable bowel syndrome. Lancet 1987; 2: 1144.
- 29 Van Op den bosch J, Van Nassauw L, Lantermann K, Van Marck E, Timmermans JP. Effect of intestinal inflammation on the cell-specific expression of somatostatin receptor subtypes in the murine ileum. Neurogastroenterol Motil 2007; 19: 596–606.
- 30 Van Op den bosch J, Lantermann K, Torfs P, Van Marck E, Van Nassauw L, Timmermans JP. Distribution and expression levels of somatostatin and somatostatin receptors in the ileum of normal and acutely Schistosoma mansoni-infected SSTR2 knockout/lacZ knockin mice. Neurogastroenterol Motil 2008; 20: 798–807.
- 31 Saavedra Y, Vergara P. Somatostatin inhibits intestinal mucosal mast cell degranulation in normal conditions and during mast cell hyperplasia. Regul Pept 2003; 111: 67–75.
- 32 Tang C, Lan C, Wang C, Liu R. Amelioration of the development of multiple organ dysfunction syndrome by somatostatin via suppression of intestinal mucosal mast cells. Shock 2005; 23: 4705.
- 33 Corsi MM, Ticozzi C, Netti C et al. The effect of somatostatin on experimental inflammation in rats. Anesth Analg 1997; 85: 1112–5.
- 34 Khaldi S, Gargala G, Le Goff L et al. Cryptosporidium parvum isolate-dependent post-infectious jejunal hypersensitivity and mast cell accumulation in an immunocompetent rat model. Infect Immun 2009; 77: 5163–9.
- 35 Marion R, Baishanbo A, Gargala G et al. Transient neonatal Cryptosporidium parvum infection triggers long-term jejunal hypersensitivity to distension in immunocompetent rats. Infect Immun 2006; 74: 4387–9.
- 36 Auray G, Lacroix-Lamande S, Mancassola R, Dimier-Poisson I, Laurent F. Involvement of intestinal epithelial cells in dentritic cell recruitment during Cryptosporidium parvum infection. Microbes Infect 2007; 9: 574–82.
- 37 Lacroix-Lamande S, Mancassola R, Naciri M, Laurent F. Role of gamma interferon in chemokine expression in the ileum of mice and in a murine intestinal epithelial cell line after Cryptosporidium parvum infection. Infect Immun 2002; 70: 2090–9.
- 38 Topouchian A, Huneau JF, Barbot L et al. Evidence for the absence of an intestinal adaptive mechanisms to compensate for Cryptosporidium parvum-induced amino acid malabsortion in suckling rats. Parasitol Res 2003; 91: 197–203.
- 39 Wheatcroft J, Wakelin D, Smith A, Mahoney CR, Mawe G, Spiller R. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction. Neurogastroenterol 2005; 17: 863–70.
- 40 Toupouchian A, Kapel N, Larue-Achagiotis C et al. Cryptosporidium infection impairs growth and muscular protein synthesis in suckling rats. Parasitol Res 2005; 96: 326–30.
- 41 Fioramonti J, Gebbart GF. In vivo and transgenic animal models used to study visceral hypersensitivity. Neurogastroenterol 2007; 19: 20–8.
- 42 Gay J, Fioramonti J, Garcia-Villar R, Bueno L. Alterations of intestinal motor responses to various stimuli after Nippostrongylus brasiliensis infection in rats: role of mast cells. Neurogastroenterol Motil 2000; 12: 207–14.
- 43 Mayer EA, Collins SM. Evolving pathophysiologic models of functional gastrointestinal disorders. Gastroenterology 2002; 122: 2032–48.
- 44 Morteau O, Hachet T, Caussette M, Bueno L. Experimental colitis alters visceromotor response to colorectal distension in awake rats. Dig Dis Sci 1994; 39: 1239–48.
- 45 O’Mahony SM, Marchesi JR, Scully P et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 2009; 65: 263–7.
- 46 Stead RH, Tomioka M, Quinonez G, Simon GT, Felten SY, Bienenstock J. Intestinal mucosal mast cells in normal and nematode infected rat intestines are in intimate contact with peptidergic nerves. Proc Natl Acad Sci USA 1987; 84: 2975–9.
- 47 McDonald V, Deer R, Uni S, Iseki M, Bancroft GJ. Immune responses to Cryptosporidium muris and Cryptosporidium parvum in adult immunocompetent or immunocompromised (nude and SCID) mice. Infect Immun 1992; 60: 3325–31.
- 48 Mead JR, Arrowood MJ, Sidwell RW, Healey MC. Chronic Cryptosporidium parvum infections in congenitally immunodeficient SCID and nide mice. J Infect Dis 1991; 163: 1297–304.
- 49 Rehg JE. Effect of interferon-gamma in experimental Cryptosporidium parvum infection. J Infect Dis 1996; 174: 229–32.
- 50 Robinson P, Martin P, Garza A, D’Souza M, Mastrangelo MA, Tweardy D. Substance P receptor antagonism for treatment of cryptosporidiosis in immunosuppressed mice. J Parasitol 2008; 94: 1150–4.
- 51 Trimble KC, Farouk R, Pryde A, Douglas S, Heading RC. Heightened visceral sensation in functional gastrointestinal disease is not site-specific: evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995; 40: 1607–13.
- 52 Slama A, Bluet-Pajot MT, Mounier F, Videau C, Kordon C, Epelbaum J. Effects of neonatal administration of octreotide, a long-lasting somatostatin analogue, on growth hormone regulation in the adult rat. Neuroendocrinol 1996; 63: 173–80.
- 53 Argenzio RA, Liacos JA, Levy ML, Meuten DJ, Lecce JG, Powell DW. Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose-Na absorption in enteric cryptosporidiosis of pigs. Gastroenterology 1990; 98: 1129–40.
- 54 Gookin JL, Nordone SK, Argenzio RA. Host responses to Cryptosporidium infection. J Vet Intern Med 2002; 16: 12–21.
- 55 Sherrington CS. The Integrative Action of the Nervous System. New Haven, CT: Yale University Press, 1906.
- 56 Ness TJ, Gebhart GF. Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudoaffective reflexes in the rat. Brain Res 1988; 450: 153–69.
- 57 Accarino AM, Azpiroz F, Malagelada JR. Symptomatic responses to stimulation of sensory pathways in the jejunum. Am J Physiol 1992; 263: G673–7.
- 58 Capet C, Kapel N, Huneau JF et al. Cryptosporidium parvum infection in suckling rats: impairment of mucosal permeability and Na+ glucose cotransport. Exp Parasitol 1999; 91: 119–25.
- 59 Cascini C, Lattuana D, Perego C, Franco P, Marelli O. Inhibitory effect of somatostatin on human T lymphocytes proliferation. Int J Immunopharmacol 1997; 19: 721–7.
- 60 Woodbury RG, Gruzenski GM, Lagunoff D. Immunofluorescent localization of a serine protease in rat small intestine. Proc Natl Acad Sci USA 1978; 75: 2785–9.
- 61 Harp JA, Moon HW. Susceptibility of mast cell-deficient W/Ww mice to Cryptosporidium parvum. Infect Immun 1991; 59: 718–20.
- 62 Barreau F, Ferrier L, Fioramonti J, Bueno L. Neonatal maternal deprivation triggers long-term alterations in colonic epithelial barrier and mucosal immunity in rats. Gut 2004; 53: 501–6.
- 63 McLean PG, Picard C, Garcia-Villar R et al. Role of kinin B1 and B2 receptors and mast cells in post-intestinal infection-induced hypersensitivity to distension. Neurogastroenterol 1998; 10: 499–508.
- 64 McLean PG, Picard C, Garcia-Villar R, More J, Fioramonti J, Bueno L. Effects of nematode infection on sensitivity to intestinal distension: role of tachykinin NK2 receptors. Eur J Pharmacol 1997; 337: 279–82.
- 65 Guilarte M, Santos J, de Torres I et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203–9.
- 66 Park JH, Rhee PL, Kim BS et al. Mucosal mast cell counts correlate with visceral hypersensitivityin patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol 2006; 21: 71–8.
- 67 Walker MM, Talley NJ, Prabhakar M et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 2009; 29: 765–73.
- 68 Barreau F, Salvador-Cartier C, Houdeau E, Bueno L, Fioramonti J. Long-term alterations of colonic nerve–mast cell interactions induced by neonatal maternal deprivation in rats. Gut 2008; 57: 582–90.
- 69 Reubi JC. Somatostatin receptors in the gastrointestinal tract in health and disease. Yale J Biol Med 1992; 65: 493–503.
- 70 Chey WD, Beydoun A, Roberts DJ, Hasler WL, Owyang C. Octreotide reduces perception of rectal electrical stimulation by spinal afferent pathway inhibition. Am J Physiol 1995; 269: 821–6.
- 71 Su X, Burton M, Gebhart G. Effects of octreotide on responses to colorectal distension in the rat. Gut 2001; 48: 676–82.
- 72 Rong W, Winchester WJ, Grundy D. Spontaneous hypersensitivity in mesenteric afferent nerves of mice deficient in the sst2 subtype of somatostatin receptor. Gastroenterology 2007; 581: 779–86.
- 73 Booth CE, Kirkup AJ, Hicks GA, Humphrey PPA, Grundy D. Somatostatin sst2 receptor-mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat. Gastroenterology 2001; 121: 358–69.
- 74 Van Nassauw L, Adriaensen D, Timmermans JP. The bidirectional communication between neurons and mast cells within the gastrointestinal tract. Auton Neurosci 2007; 133: 91–103.
- 75 Gibney SM, Gosselin RD, Dinan TG, Cryan JF. Colorectal distension-induced prefrontal cortex activation in the Wistar–Kyoto rat: implications for irritable bowel syndrome. Neuroscience 2010; 165: 675–83.
- 76 Mayer EA, Tillisch K, Bradesi S. Modulation of the brain-gut axis as a therapeutic approach in gastrointestinal disease. Aliment Pharm Therap 2006; 24: 919–33.
- 77 Krejs GJ. Physiological role of somatostatin in the digestive tract: gastric acid secretion, intestinal absorption, and motility. Scand J Gastroenterol 1986; 119(Suppl.): 47–53.
- 78 Tulassay Z. Somatostatin and the gastrointestinal tract. Scand J Gastroenterol 1998; 228(Suppl.): 115–21.
- 79 Guarino A, Canani RB, Spagnuolo MI, Bisceglia M, Boccia MC, Rubino A. In Vivo and in Vitro efficacy of octreotide for treatment of enteric cryptosporidiosis. Digest Dis Sci 1998; 43: 436–41.
- 80 Bouin M, Lupien F, Riberdy M, Boivin M, Plourde V, Poitras P. Intolerance to visceral distension in functional dyspesia or irritable bowel syndrome: an organ specific defect or a pan intestinal dysregulation? Neurogastroenterol Motil 2004; 16: 311–4.
- 81 Klooker TK, Kuiken SD, Lei A, Boeckxstaens GE. Effect of long-term treatment with octreotide on rectal sensitivity in patients with non-constipated irritable bowel syndrome. Aliment Pharm Therap 2007; 26: 605–15.