title: Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation.
abstract: Diabetes has been identified as an important risk factor for infection. But relatively little is known about how diabetes alters the inflammatory response to bacteria. The objective of this study was to investigate how diabetes affects host-bacteria interactions by focusing on the inflammatory response in a connective tissue setting. Diabetic (db/db) and control (db/+) mice were inoculated with Porphyromonas gingivalis, a pathogen associated with bite wounds and periodontal disease. The response was measured histologically or by the expression of inflammatory cytokines. By quantitative histologic analysis, there was little difference between the diabetic and control mice on day 1. On day 3, however, the inflammatory infiltrate had subsided in the control group, whereas it had not in the diabetic group (p<0.05). Similar results were noted at the molecular level by the persistent expression of tumor necrosis factor-alpha (TNF-alpha) and the chemokines MCP-1 and MIP-2. The importance of TNF in this process was demonstrated by reversal of the prolonged chemokine expression by specific inhibition of TNF with Enbrel. These results indicate that cytokine dysregulation associated with prolonged TNF expression represents a mechanism through which bacteria may induce a more damaging inflammatory response in diabetic individuals.
authors.affiliation: Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Ghada
authors.initials: G
authors.lastname: Naguib
authors.forename: Hesham
authors.initials: H
authors.lastname: Al-Mashat
authors.forename: Tesfahun
authors.initials: T
authors.lastname: Desta
authors.forename: Dana T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D006943:Hyperglycemia / Q000150:complications / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016966:Porphyromonas gingivalis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha