title: A role for IL-1 alpha in inducing pathologic inflammation during bacterial infection.
abstract: Infection with pathogenic microbes often results in a significant inflammatory response. A cascade of proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and IL-1 initiates this response. Although there is a clear role for IL-1 during infection, little is known to distinguish the role of IL-1 alpha from that of IL-1 beta during this process. With the use of Yersinia enterocolitica as a model enteric pathogen, we have identified a specific role for IL-1 alpha in inducing pathologic inflammation during bacterial infection. Depletion of IL-1 alpha in mice infected with wild-type Y. enterocolitica results in significantly decreased intestinal inflammation. Furthermore, a bacterial mutant that does not induce IL-1 alpha expression but induces normal levels of IL-1 beta, TNF-alpha, and IFN-gamma, causes greatly reduced intestinal inflammation and is attenuated by LD(50) analysis in the C57BL/6 mouse model. These results demonstrate a distinct and unrecognized role for IL-1 alpha in inducing intestinal inflammation that cannot be compensated for by the endogenous levels of IL-1 beta, TNF-alpha, or IFN-gamma that are produced in response to Y. enterocolitica. Additionally, these results suggest that IL-1 alpha-induced inflammation is a major contributor to the pathology of yersiniosis.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Dube
authors.forename: P A
authors.initials: PA
authors.lastname: Revell
authors.forename: D D
authors.initials: DD
authors.lastname: Chaplin
authors.forename: R G
authors.initials: RG
authors.lastname: Lorenz
authors.forename: V L
authors.initials: VL
authors.lastname: Miller
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015009:Yersinia Infections / Q000276:immunology* / Q000473:pathology; D015008:Yersinia enterocolitica / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D007375:Interleukin-1; C405626:RovA protein, Yersinia; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma