Immunomodulating Effects of OM-89, a Bacterial Extract from Escherichia coli, in Murine and Human Leukocytes

Abstract

OM-89 (Uro-Vaxom®) is a bacterial extract prepared from 18 uropathogenic Escherichia coli strains used for the prevention and treatment of recurrent infections of the urinary tract. The immunomodulating effects of the bacterial extract were investigated in a mouse model. After a single oral administration of OM-89, leukocyte activation was demonstrated ex vivo in blood and liver cells using a chemiluminescence assay. An increase of the production of tumor necrosis factor-α (TNF-α) in supernatants of peritoneal cells was also observed. After repeated oral administration of OM-89, increased serum immunoglobulin G responses against several E. coli strains were found. Also, adjuvant properties of the extract using ovalbumin as an antigen could be demonstrated. In line with these findings in the mouse system, preliminary in vitro data obtained in the human system showed an increase in TNF-α and interleukin-6 production after stimulation of monocyte derived dendritic cells with OM-89. The activation of immune cells is likely to be mediated via Toll like receptors (TLRs); thus, the binding of components of the extract to TLR-4 and marginally to TLR-2 could be shown.

Key words

Bacterial extract - Dendritic cells - Immunomodulator - OM-89 - Urinary tract - Uro-Vaxom® - Vaccination

• References

• 1 Frey C, Obolenski W, Wyss H. Treatment of recurrent urinary tract infections: efficacy of an orally administered biological response modifier. Urol Int. 1986; 41: 444-6
• 2 Hachen HJ. Oral immunotherapy in paraplegic patients with chronic urinary tract infections: a double-blind, placebo-controlled trial. J Urol. 1990; 143: 759-63
• 3 Tammen H. Immunobiotherapy with Uro-Vaxom in recurrent urinary tract infection. Br J Urol. 1990; 65: 6-9
• 4 Schulman CC, Corbusier A, Michiels H, Taenzer HJ. Oral immunotherapy of recurrent urinary tract infections: a double-blind placebo-controlled multicenter study. J Urol. 1993; 150 (3) 917-21
• 5 Magasi P, Panovics J, Illes A, Nagy M. Uro-Vaxom and the management of recurrent urinary tract infection in adults: a randomized multicenter double-blind trial. Eur Urol. 1994; 26 (2) 137-40
• 6 Bauer HW, Alloussi S, Egger G, Blumlein HM, Cozma G, Schulman CC. on behalf of Multicenter UTI Study Group. A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients with recurrent urinary tract infections. Eur Urol. 2005; 47 (4) 542-8
• 7 Bosch A, Benedi KJ, Pares R. Enhancement of the humoral immune response and resistance to bacterial infection in mice by the oral administration of a bacterial immunomodulator (OM-89). Immunopharmacol Immunotoxicol. 1988; 10: 333-43
• 8 Wybran J, Libin M, Schandene L. Enhancement of cytokine production and natural killer activity by an Escherichia coli extract. Immunopharmacol Immunotoxicol. 1989; 11: 17-32
• 9 Bessler WG, Beck P, Konetznick U, Loleit M, Sedelmeier E, Hoffmann P, Strecker M, Stöcklin S. Biological activities of bacterial surface components: immunogenicity and immunomodulatory properties of a bacterial extract from Escherichia coli. Arzneimittelforschung. 1991; 41 (3) 274-9
• 10 Huber M, Ayoub M, Pfannes S, Mittenbühler K, Weis K, Eckert M et al. Immunostimulatory activity of the bacterial extract OM-89. Eur J Med Res. 2000; 5: 101-9
• 11 Bessler WG, Kleine B, Martinez A, Biesert L, Strecker M, Wiesmüller K et al. Biological activity of bacterial surface components: bacterial extracts and defined bacterial cell wall components as immunmodulators. Lung. 1990; 168: 707-15
• 12 Sedelmeier E, Bessler WG. Biological activity of bacterial cell wall components: immunogenicity of the bacterial extract OM-89. Immunopharmacology. 1995; 29: 29-36
• 13 Huber M, Baier W, Serr A, Bessler WG. Immunogenicity of an E. coli extract after oral or intraperitoneal administration: Induction of antibodies against pathogenic bacterial strains. Int J Immunopharmacol. 2000; 22: 57-68
• 14 Baier W, Huber M, Bessler WG. Oral immunization with a bacterial extract: induction of a specific humoral immune response. Immunobiol. 1997; 197: 338-9
• 15 Huber M, Krauter K, Winkelmann G, Bauer HW, Rahlfs VW, Lauener PA et al. Immunostimulation by bacterial components: II. Efficacy studies and meta-analysis of the bacterial extract OM-89. Int J Immunopharmacol. 2000; 22: 1103-11
• 16 Gaisbauer M, Schleich Th, Stickl HA, Wilczek I. [Studies on the effect of Echinacea prupurea Moench on phagocytosis activity of granulocytes using chemiluminescence measurement]. Arzneimittelforschung. 1990; 40 (5) 594-8
• 17 Baier W, Sedelmeier E, Bessler WG. Studies on the immunogenicity of an Escherichia coli extract after oral application in mice. Arzneimittelforschung. 1997; 47 (8) 980-5
• 18 Schreurs J. Cytokines in infectious disease: the battle between host and pathogen. Curr Opin Biotechnol. 1993; 4 (6) 727-33
• 19 Nacy CA, Meierovics AI, Belosevic M, Green SJ. Tumor necrosis factor-alpha: central regulatory cytokine in the induction of macrophage antimicrobial activities. Pathobiology. 1991; 59 (3) 182-4
• 20 Hockertz S. Immunomodulating effect of lysed immunoactive fractions of selected Escherichia coli strains on the macrophage system. An in vitro study. Arzneimittelforschung. 1990; 40 (9) 1068-72
• 21 Bloemendal R, van der Zee R, Rutten VPMG, van Kooten PJS, Farine JC, van Eden W. Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell response to heat shock protein hsp 60 and hsp 70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatic arthritis (RA). Clin Exp Immunol. 1997; 110: 72-8
• 22 Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18: 767-811
• 23 Banchereau J, Pulendran B, Steinman R, Palucka K. Will the making of plasmacytoid dendritic cells in vitro help unravel their mysteries?. J Exp Med. 2000; 192 (12) 39-44
• 24 Lanzavecchia A. Mechanisms of antigen uptake for presentation. Curr Opin Immunol. 1996; 8 (3) 348-54
• 25 Schmidhammer S, Ramoner R, Holtl L, Bartsch G, Thurner M, Zelle-Rieser C. An Escherichia coli-based oral vaccine against urinary tract infections potently activates human dendritic cells. Urology. 2002; 60 (3) 521
• 26 Meng G, Grabiec A, Vallon M, Ebe B, Hampel S, Bessler WG et al. Cellular recognition of tri-/di-palmitoylated peptides is independent from a domain encompassing the N-terminal seven leucine-rich repeat LRR/LRR-like motifs of TLR2 . J Biol Chem. 2003; 278: 39822-9