IL-18 is a pro-inflammatory cytokine that is important in theregulation of T-cells and is elevated in inflammatory disorderssuch as periodontal disease. Vasoactive intestinal peptide (VIP)modulates immune responses to the periodontal pathogen Porphyromonasgingivalis (Pg). Our objective was to investigate the effectof Pg LPS on IL-18 and its natural inhibitor, IL-18 bindingprotein (IL-18BPa), in human monocytes, and the effect of VIPon this system. We demonstrated that Pg LPS induced both IL-18and IL-18BPa secretion in cultures of the human monocytic cellline THP-1, as measured by specific ELISA. The addition of antibodiesto IL-18BPa to the stimulated THP-1 cultures resulted in increasedlevels of free IL-18, indicating a specific interaction betweenIL18 and IL-18BPa in this system. VIP (10–8M) inhibitedboth IL-18 and IL-18Bpa secretion by stimulated monocytes. Weconclude that IL-18 and IL-18BPa secretion by monocytes is partof the immune response to Pg, and that VIP can inhibit thisprocess.