title: Cellular and humoral systemic and mucosal immune responses stimulated by an oral polybacterial immunomodulator in patients with chronic urinary tract infections.
abstract: An oral polybacterial immunomodulator Urostim (U), composed of killed cells and their lysates from E. coli expressing type 1 and Pili, E. coli Rc mutant, P. mirabilis, K. pneumoniae and E. faecalis was created for immunoprophylaxis and immunotherapy of urinary tract infections (UTIs). In experimental animal models, the stimulating effect of U on lymphocyte functional activity, macrophage phagocytosis and antibody producing cells, was established. In this study the immuno-modulating effects of U on the proliferating capacity and ultrastructural morphologic changes of lymphocytes, cytokine production and specific systemic humoral and mucosal immune responses in patients with UTIs have been evaluated. Patients enrolled in the study, received orally 50 mg U daily for a period of three months. On days 0, 30 and 90 a quantitative analysis was performed on lymphoproliferative responses to polyclonal mitogens, IL-2 and the specific antigen U, the production of specific serum and saliva IgA, IgM and IgG antibodies to all components of U and the concentration of pro-inflammatory cytokines. There was significant improvement of non-specific and specific lymphoproliferative responses on days 30 and 90 after the onset of treatment with U, confirmed by electronmicroscopic studies. The highest concentrations of serum proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 were registered at baseline followed by a decrease until the end of the observation period. This finding correlates with the gradual decrease of immune activation as measured by the spontaneous lymphocyte proliferation. Data from the production of specific antibacterial antibodies in serum and saliva show two types of reactions. The first type was registered in patients with low pre-treatment levels in whom the concentration of specific antibodies increased on days 30 and 90. The second type of reaction was observed in patients with high pre-treatment levels, which dropped on day 30 and were usually followed by an increase at the end of the study. These results provide evidence for the immuno-modulating effect of U. Our data show that the oral administration of the polybacterial immunomodulator Urostim stimulates adequate cellular and humoral systemic and mucosal immune responses in patients with chronic UTIs.
authors.affiliation: National Center of Infectious and Parasitic Diseases (NCIPD), Sofia, Bulgaria.
authors.forename: S
authors.initials: S
authors.lastname: Marinova
authors.forename: P
authors.initials: P
authors.lastname: Nenkov
authors.forename: R
authors.initials: R
authors.lastname: Markova
authors.forename: S
authors.initials: S
authors.lastname: Nikolaeva
authors.forename: R
authors.initials: R
authors.lastname: Kostadinova
authors.forename: I
authors.initials: I
authors.lastname: Mitov
authors.forename: M
authors.initials: M
authors.lastname: Vretenarska
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D013997:Time Factors; D014552:Urinary Tract Infections / Q000276:immunology* / Q000628:therapy*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D016207:Cytokines; D007376:Interleukin-2; D008934:Mitogens; D017778:Vaccines, Combined; C097060:urostim