title: Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune responses in human monocytes infected with viable Salmonella or stimulated with LPS.
abstract: We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10(-7)M) increased monocyte viability by 24% and 9% when cultured for 24h with 4/74 or Salmonella LPS (100ng/ml), respectively. Significantly increased (P<0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6h post-infection (pi) and this remained high after 24h pi. Both 4/74 and LPS increased (P<0.05) the concentration of TNF-α, IL-1β and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations (P<0.05). VIP significantly decreased (P<0.05) TNF-α and IL-1β production by 4/74-infected monocytes after 6 pi, but only after 24h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-α and IL-1β production by 4/74-infected monocytes, cultured with VIP, still remained higher (P<0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased (P<0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24h. We also show a differential effect of VIP on the expression of TNFα and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes. In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.
authors.forename: Basim
authors.initials: B
authors.lastname: Askar
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.
authors.forename: Hiba
authors.initials: H
authors.lastname: Ibrahim
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Barrow
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK. Electronic address: n.foster@nottingham.ac.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Foster
mesh_terms: D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015846:Monokines / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D015846:Monokines; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014660:Vasoactive Intestinal Peptide
keywords: Human monocytes; Salmonella; VIP