In Vivo and in Vitro Efficacy of Octreotide for Treatment of Enteric Cryptosporidiosis

Abstract

Previous evidence suggested a role of enterotoxin in the pathophysiology of cryptosporidiosis. If so, antisecretory drugs should be effective in reducing diarrhea. We evaluated the in vivo and in vitro efficacy of octreotide, which possesses antisecretory effects, for cryptosporidial diarrhea. Two children with severe cryptosporidial diarrhea were treated with octreotide. The volume modifications and chemical composition of stools were determined. Fecal supernatant was added to Caco-2 cell monolayers mounted in Ussing chambers with or without serosal octreotide and electrical parameters were monitored. Octreotide was effective in reducing the stool volume and fecal Na concentration. Fecal supernatant induced an enterotoxin-like increase in transepithelial potential difference. Octreotide induced a dosedependent decrease in basal potential difference, consistent with an absorptive effect. In cells pretreated with octreotide, fecal supernatant induced an increase in the potential difference, whose magnitude and duration were significantly reduced compared to untreated cells. These results provide in vivo and in vitro evidence for the secretory nature of cryptosporidial diarrhea and for the efficacy of octreotide through a direct interaction with the enterocyte.

This is a preview of subscription content, access via your institution.

REFERENCES

  1. 1.

    Adal KA, Sterling CR, Guerrant RL: Cryptosporidiumand related species. InInfections of the Gastrointestinal Tract. MJ Blaser, PD Smith, JI Ravdin, RL Guerrant (eds). New York, Raven Press, 1995, pp 1107- 1128

    Google Scholar 

  2. 2.

    Guarino A, Spagnuolo MI, Russo S, Albano F, Guandalini S, Capano G, Cucchiara S, Vairano P, Liguori R, Casola A, Rubino A: Etiology and risk factors of severe and protracted diarrhea. J Pediatr Gastroenterol Nutr 20:173- 178, 1995

    Google Scholar 

  3. 3.

    Guarino A, Berni Canani R, Pozio E, Terracciano L, Albano F, Mazzeo M: Enterotoxic effect of stool supernatant of Cryptosporidiuminfected calves on human jejunum. Gastroenterology 106:28 - 34, 1994

    Google Scholar 

  4. 4.

    Guarino A, Berni Canani R, Casola A, Pozio E, Russo R, Bruzzese E, Fontana M, Rubino A: Human intestinal cryptosporidiosis: secretory diarrhea and enterotoxic activity in Caco-2 cells. J Infect Dis 171:976 - 983, 1995

    Google Scholar 

  5. 5.

    Field M, Rao MC, Chang EB: Intestinal electrolyte transport and diarrheal disease (first of two parts). N Engl J Med 21:800 - 806, 1989

    Google Scholar 

  6. 6.

    Montaner JSG, Harris AG, Octreotide International Multicentre AIDS/Diarrhea Study Group: Octreotide therapy in AIDS-related, refractory diarrhea: Results of a multicentre Canadian - European study. AIDS 9:209 - 210, 1995

    Google Scholar 

  7. 7.

    Harris AG, D'Orisio TM, Woltering EA, Anthony LB, Burton FR, Geller RB, Grendell JH, Levin B, Redfern JS: Consensus statement: Octreotide dose titration in secretory diarrhea. Diarrhea management consensus development panel. Dig Dis Sci 40:1464 - 1473, 1995

    Google Scholar 

  8. 8.

    Lamberts SWJ, Van der Lely AJ, De Herder WW, Hofland LJ: Octreotide. N Engl J Med 334:246 - 254, 1996

    Google Scholar 

  9. 9.

    Gomez-Morales MA, Ausiello CM, Guarino A, Urbani F, Pignata C, Spagnuolo MI, Pozio E: Severe, protracted intestinal cryptosporidiosis associated with interferon-γ deficiency: Pediatric case report. Clin Infect Dis J 22:848 - 850, 1996

    Google Scholar 

  10. 10.

    Cook DJ, Ke lton JG, Stanisz AM, Collins SM: Somatostatin treatment for cryptosporidial diarrhea in a patient with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 108:708 - 709, 1988

    Google Scholar 

  11. 11.

    Edwards CA, Cann PA, Read NW, Holdsworth CD: The effect of somatostatin analogue SMS 201-885 on fluid and electrolyte transport in a patient with secretory diarrhea. Scand J Gastroenterol 21( suppl 119):259 - 261, 1986

    Google Scholar 

  12. 12.

    Ohlbaum Ph, Galperine RI, Demarquez JL, Vergnes P, Martin CL: Use of a long acting somatostatin analogue (SMS 201-995) in controlling a significant ileal output in a 5-year-old child. J Pediatr Gastroenterol Nutr 6:466 - 470, 1987

    Google Scholar 

  13. 13.

    Johansson C, Efendic S, Wisen O, Uvnas-Wallenstein K, Luft R: Effects of short time somatostatin infusion on the gastric and intestinal propulsion in humans. Scand J Gastroenterol 13:481- 483, 1978

    Google Scholar 

  14. 14.

    Carter RF, Bitar KN, Zfass AM, Markhlouf GM: Inhibition of VIP-stimulated intestinal secretion and cAMP production by somatostatin in the rat. Gastroenterology 74:726 - 730, 1978

    Google Scholar 

  15. 15.

    Ruskone A, Rene E, Chayvialle JA: Effect of somatostatin on diarrhea and on small intestinal water and electrolyte transport in a patients with pancreatic cholera. Dig Dis Sci 27:459 - 466, 1982

    Google Scholar 

  16. 16.

    Guentar JK, Brown R, Raskin P: Effect of intravenous somatostatin on jejunal absorption of glucose, amino acid, water and electrolyte. Gastroenterology 78:26 - 31, 1980

    Google Scholar 

  17. 17.

    Dharmasathaphorn K, Sherwin RS, Dobbins JW: Somatostatin inhibits fluid secretion in the rat jejunum. Gastroenterology 78:1554 - 1558, 1980

    Google Scholar 

  18. 18.

    Fassler JE, D'Orisio TM, Mekhjian HS, Gaginella TS: Octreotide inhibits increases in short circuit current induced in rat colon by VIP, substance P, serotonin and aminophylline. Regul Pept 29:189 - 197, 1990

    Google Scholar 

  19. 19.

    Diener M, Gartman V: Effect of somatostatin on cell volume, Cl- currents, and transepithelial Cl- transport in rat distal colon. Am J Physiol 266:G1043- G1052, 1994

    Google Scholar 

  20. 20.

    Guandalini S, Kachur JF, Smith PL, Miller RJ, Field M: In vitroeffect of somatostatin on ion transport in rabbit intestine. Am J Physiol 238:G67- G74, 1980

    Google Scholar 

  21. 21.

    Bisse t WM, Jenkins H, Booth I, Smith V, Milla PJ: The effect of somatostatin on small intestinal transport in intractable diarrhoea in infancy. J Pediatr Gastroenterol Nutr 17:169 - 175, 1993

    Google Scholar 

  22. 22.

    Couper R, Frischman W: Somatostatin and small intestinal transport. J Pediatr Gastroenterol Nutr 19:137- 138, 1994

    Google Scholar 

  23. 23.

    Cello JP, Grendell JH, Basuk P, Simon D, Weiss L, Wittner M, Rood RP, Wilcox CM, Forsmark CE, Read AE: Effect of octreotide on refractory AIDS-associated diarrhea: A prospective multicenter clinical trial. Ann Intern Med 115:705- 710, 1991

    Google Scholar 

  24. 24.

    Harris AG: Octreotide in the treatment of disorders of the gastrointestinal tract. Drug Invest 4:1- 54, 1992

    Google Scholar 

  25. 25.

    Romeu J, Miro JM, Sirera G, Mallolas J, Arnal J, Valls ME, Tortosa F, Clotet B, Foz M: Efficacy of octreotide in the management of chronic diarrhoea in AIDS. AIDS 5:1495- 1499, 1991

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Guarino, A., Canani, R.B., Spagnuolo, M.I. et al. In Vivo and in Vitro Efficacy of Octreotide for Treatment of Enteric Cryptosporidiosis. Dig Dis Sci 43, 436–441 (1998). https://doi.org/10.1023/A:1018839329759

Download citation

  • CRYPTOSPORIDIUM
  • ENTEROTOXIN
  • HIV INFECTION
  • OCTREOTIDE
  • SOMATOSTATIN
  • DIARRHEA