title: Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance.
abstract: Ulcerative colitis (UC) and Crohn's disease (CD) [inflammatory bowel disease (IBD)] are both characterized by an exaggerated immune response at the gut associated lymphoreticular tissue level. Such an abnormal and dysregulated immune response may be directed against luminal and/or enteric bacterial antigens, as also supported by murine models of inflammatory bowel disease (IBD) caused by organisms such as Citrobacter rodentium and Helicobacter hepaticus. Bacterial endotoxins or lipopolysaccharides (LPS) have been detected in the plasma of IBD patients and an abnormal microflora and/or an increased permeability of the intestinal mucosa have been invoked as cofactors responsible for endotoxemia. At the same time, the evidence that phagocytosis and killing exerted by polymorphonuclear cells and monocytes and the T-cell dependent antibacterial activity are decreased in IBD patients may also explain the origin of LPS in these diseases. In IBD, pro-inflammatory cytokines and chemokines have been detected in elevated amounts in mucosal tissue and/or in peripheral blood, thus suggesting a monocyte/macrophage stimulation by enteric bacteria and/or their constituents (e.g. LPS). On these grounds, in experimental models and in human IBD, anti-cytokine monoclonal antibodies and interleukin receptor antagonists are under investigation for their capacity to neutralize the noxious effects of immune mediators. Finally, the administration of lactobacilli is beneficial in human IBD and, in murine colitis, this treatment leads to a normalization of intestinal flora, reducing the number of colonic mucosal adherent and translocated bacteria.
authors.affiliation: Scientific Institute for Gastrointestinal Diseases, Castellana Grotte, Bari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Caradonna
authors.forename: L
authors.initials: L
authors.lastname: Amati
authors.forename: T
authors.initials: T
authors.lastname: Magrone
authors.forename: N M
authors.initials: NM
authors.lastname: Pellegrino
authors.forename: E
authors.initials: E
authors.lastname: Jirillo
authors.forename: D
authors.initials: D
authors.lastname: Caccavo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000097:blood; D016971:Citrobacter freundii / Q000472:pathogenicity; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D006090:Gram-Negative Bacteria / Q000737:chemistry* / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000276:immunology; D016998:Helicobacter / Q000472:pathogenicity; D006801:Humans; D007111:Immunity, Cellular; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000382:microbiology; D007778:Lactobacillus; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D010587:Phagocytosis
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D008070:Lipopolysaccharides