title: Polybacterial immunomodulator Respivax restores the inductive function of innate immunity in patients with recurrent respiratory infections.
abstract: Respivax (BulBio-NCIPD Ltd.) is an oral polybacterial immunomodulator intended for treatment and prevention of non-specific respiratory tract infections. We studied for the first time its effects on the inductive mechanisms of innate immunity, in the course of 3-month immunoprophylaxis of 25 patients with recurrent and chronic respiratory infections. The expression of pattern-recognition receptors on peripheral blood (PB) monocytes and plymorphonuclear cells (PMNs), the antigen-presenting and co-stimulatory potential of peripheral blood monocytes and dendritic cells; and the stimulated Th1/Th2 cytokine production were determined by flow cytometry. As compared to healthy controls, patients were characterized with down-regulation of TLR2 and TLR4/CD14 complex on PB monocytes (p<0.01), decreased share of CD14+CD16+ DCs precursors (p<0.01), decreased CD86 expression on PB DCs (p<0.05) and a Th2 shift of cytokine profile. Respivax modulated differentially the surface expression of pattern-recognition receptors on PB monocytes, increasing TLR2 and CD14 without affecting TLR4 expression. Further on, Respivax enhanced the differentiation of mature CD86(high) dendritic cells (DCs). Importantly, Respivax promoted a Th1 shift of cytokine profile and restored the Th1/Th2 cytokine balance without pro-inflammatory effects. Noteworthy, Th1/Th2 ratios in the patient's group correlated positively with the levels of TLR2 (R=0.5, p<0.001) and CD14 expression (R=0.4, p<0.05). We conclude that Respivax treatment restores the inductive function of innate immunity at three key levels: antigen recognition and presentation, co-stimulation of naïve T cells, and Th1/Th2 balance. This results, at least in part, from a differential modulation effect on the expression of pathogen-recognition receptors.
authors.affiliation: Department of Immunology and Allergology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria.
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolova
authors.forename: Draganka
authors.initials: D
authors.lastname: Stankulova
authors.forename: Hristo
authors.initials: H
authors.lastname: Taskov
authors.forename: Plamen
authors.initials: P
authors.lastname: Nenkov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Maximov
authors.forename: Bogdan
authors.initials: B
authors.lastname: Petrunov
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D055502:Secondary Prevention; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D016207:Cytokines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C060965:respivax