Inflammatory bowel diseases (IBD) have become a significant public health problem due to the increase in the incidence of IBD, particularly Crohn's disease, in the U.S. population. The etiology of IBD is still unknown, however, previous studies, certain clinical manifestations and preliminary findings presented in this proposal give us clues to the possible mechanisms involved. Specifically, patients with IBD exhibit depressed neutrophil chemotactic function in vitro. Concomitantly, severe periodontal disease has been noted as a characteristic feature in certain IBD patients. This is not surprising since the neutrophil is an important cell in host resistance to periodontal breakdown. Since periodontitis is an infectious disease, we investigated the periodontal microflora of IBD patients and found it to be unique and uncharacteristic of periodontal diseases. The IBD periodontal microflora is composed almost completely of a small (less than 0.2u) motile, anaerobic Gram negative rod. It is the purpose of this study to begin characterizing the relationships between neutrophil abnormalities, infectious agents and the pathogenesis of IBD. This will be accomplished by elucidating the biochemical basis for neutrophil dysfunction and determining the role of the host microflora. 1) The neutrophil functions of chemotaxis, phagocytosis and bactericidal activity will be measured using standard in vitro techniques. The molecular basis of alterations in neutrophil function will be assayed using studies of binding of biologically active molecules to the neutrophil surface, characterization of the C5a receptor, evaluation of surface protein and glycoprotein content and investigation of serum inhibitors. 2) Bacterial factors that may effect neutrophil function will be evaluated. 3) The nature and extent of periodontal disease in IBD patients will be correlated to IBD disease activity. 4) Serum antibody titers to predominant gut and periodontal microorganisms will be determined and longitudinally monitored for correlation to changes in disease activity. The goal of these investigations is to gain further knowledge of the structural and functional relationships of the inflammatory process by defining the complex interactions between the neutrophil and its environment, particularly microorganisms. The investigation of unique anaerobic microbes, in relation to neutrophil dysfunction, presents an opportunity to gain further insight into the etiology and pathogenesis of IBD.