Immunomodulation by vasoactive intestinal peptide is associated with increased survival and growth of Salmonella Typhimurium in mice

Askar, Basim; Higgins, John; Barrow, Paul; Foster, Neil

Abstract

© 2019 Elsevier Ltd Studies have shown that administration of vasoactive intestinal peptide (VIP) in mice rescues them from lethal endotoxaemia and that this is correlated with decreased concentration of inflammatory cytokines. VIP has, therefore, been proposed as a novel anti-inflammatory which could be used in the treatment of Gram negative sepsis. However, the effect of VIP has not been reported in mice infected with viable Gram negative bacteria. Here, we show that Salmonella enterica serovar Typhimurium 4/74 significantly increased expression of mRNA of a type 1 receptor (VPAC1) for anti-inflammatory vasoactive intestinal peptide (VIP) in murine ileum and mesenteric lymph nodes at day 6 post-infection (d6 pi) and in the spleen at d3 pi. When VIP (5 nmol/ml) was administered to S. Typhimurium-infected mice, there was a significant increase in the number of S. Typhimurium cultured from murine faeces and ileum at d3 and 6 pi and in MLN and spleen at d3 dpi, compared to faeces and tissues examined from mice infected with S. Typhimurium (without VIP administration). Administration of VIP to S. Typhimurium-infected mice also altered the splenic architecture, resulting in a lack of discernable periarterial lymphoid sheaths or marginal zones at d6 pi but liver histology appeared similar on both d3 and d6 pi. The effects of VIP administration were correlated with a significant decrease in expression of inflammatory cytokine mRNA, associated with systemic inflammatory response syndrome (SIRS) of bacteraemia and acute sepsis. We conclude that VIP inhibits expression of diagnostic/prognostic cytokine biomarkers of sepsis in S. Typhimurium-infected mice. However, this occurred with a concomitant increase in Salmonella growth in tissues and increased bacterial shedding in faeces. Thus, VIP may have potential as an adjunctive therapy to antibiotics in sepsis.

Citation

Askar, B., Higgins, J., Barrow, P., & Foster, N. (2020). Immunomodulation by vasoactive intestinal peptide is associated with increased survival and growth of Salmonella Typhimurium in mice. Cytokine, 125, Article 154787. https://doi.org/10.1016/j.cyto.2019.154787

• Journal Article Type: Article
• Acceptance Date: Jul 22, 2019
• Online Publication Date: Aug 9, 2019
• Publication Date: 2020-01
• Deposit Date: Aug 5, 2019
• Publicly Available Date: Aug 10, 2020
• Journal: Cytokine
• Print ISSN: 1043-4666
• Electronic ISSN: 1096-0023
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 125
• Article Number: 154787
• DOI: https://doi.org/10.1016/j.cyto.2019.154787
• Keywords: Immunology; Immunology and Allergy; Biochemistry; Molecular Biology; Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/2391707
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1043466619302169
• Additional Information: This article is maintained by: Elsevier; Article Title: Immunomodulation by vasoactive intestinal peptide is associated with increased survival and growth of Salmonella Typhimurium in mice; Journal Title: Cytokine; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.cyto.2019.154787; Content Type: article; Copyright: © 2019 Elsevier Ltd. All rights reserved.