Interaction of Vasoactive Intestinal Peptide with Lipopolysaccharide of Prevotella denticola

Vasoactive Intestinal peptide (VIP) is produced by lymphoid cells and shown to suppress the production of inflammatory cytokines when monocytes are stimulated with bacterial LPS. Objective:  Determine the effect of VIP on the secretion of inflammatory cytokines by monocytic cells when stimulated with P. denticola (Pd) LPS. Methods: Pro-monocytic THP-1 cells were cultured and differentiated by incubating the cells with PMA for 48 h.  The cells (5x10⁵) in triplicate, were incubated with Pd LPS (10ng/ml) or with a mixture of LPS and VIP (10^-8 M) for 24 h at 37°C. Culture supernatants were collected and assayed for the secreted IL-18 and TNF-alpha using the ELISA kits (R and D Systems) according to the protocol recommended by the manufacturer. Results: Pd LPS stimulated monocytes to secrete significantly lower amounts of cytokines, when compared to the stimulation seen with control LPS of E. coli. THP-1 cells secreted 850 and 320 pg/ml of TNF-alpha and IL-18, respectively when stimulated with Pd LPS, while Ec LPS stimulation resulted in 1820 and 862 pg/ml of the same cytokines. Furthermore, monocytes incubated with LPS+VIP secreted less cytokines, IL-18 secretion was reduced by 70%, and TNF-alpha by 62%. VIP was also efficient in inhibiting secretion of cytokines when the THP-1 cells were stimulated with LPS of E. coli. Conclusion: The inflammatory response of THP-1 cells to LPS Pd and Ec was inhibited by VIP, similar observation by other researchers made with other bacterial LPS.  Based on this observation, it could be speculated that VIP may be a beneficial therapeutic agent in reducing the pro-inflammatory reactions associated with LPS of periodontal bacteria and may control the severity of periodontal disease.

Supported by the UTHSC Dental Alumni Endowment Fund for Research.