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VIP Inhibits P. gingivalis LPS-induced IL-18 and IL-18BPa in Monocytes

Oral Microbiology and Host Responses Group, Oral Biology, School of Dental Sciences, University of Newcastle upon Tyne, NE2 4BW, UK

² corresponding author, j.j.taylor{at}ncl.ac.uk

IL-18 is a pro-inflammatory cytokine that is important in the regulation of T-cells and is elevated in inflammatory disorders such as periodontal disease. Vasoactive intestinal peptide (VIP) modulates immune responses to the periodontal pathogen Porphyromonas gingivalis (Pg). Our objective was to investigate the effect of Pg LPS on IL-18 and its natural inhibitor, IL-18 binding protein (IL-18BPa), in human monocytes, and the effect of VIP on this system. We demonstrated that Pg LPS induced both IL-18 and IL-18BPa secretion in cultures of the human monocytic cell line THP-1, as measured by specific ELISA. The addition of antibodies to IL-18BPa to the stimulated THP-1 cultures resulted in increased levels of free IL-18, indicating a specific interaction between IL18 and IL-18BPa in this system. VIP (10^–8M) inhibited both IL-18 and IL-18Bpa secretion by stimulated monocytes. We conclude that IL-18 and IL-18BPa secretion by monocytes is part of the immune response to Pg, and that VIP can inhibit this process.

KEY WORDS: IL-18 • IL-18 BPa • Porphyromonas gingivalis • LPS • VIP