Protective role of interleukin-6 during Yersinia enterocolitica infection is mediated through the modulation of inflammatory cytokines.
Yersinia enterocolitica is a gram-negative enteric pathogen responsible for a number of gastrointestinal disorders. A striking feature of the pathology of a Y. enterocolitica infection is inflammation. Recently, we demonstrated a role for interleukin-1alpha (IL-1alpha) in the establishment of intestinal inflammation in response to a Y. enterocolitica infection. A cytokine directly affected by IL-1 levels is IL-6. A previous report suggested that IL-6 plays an anti-inflammatory role during Y. enterocolitica infection, and in other systems IL-6 has been shown to be proinflammatory. Therefore, a closer examination of the roles of IL-6 and inflammatory cytokines in the control of Y. enterocolitica infection in IL-6(-/-) mice was undertaken. Y. enterocolitica organisms were more virulent in the IL-6(-/-) mice (60-fold decreased 50% lethal dose) and colonized systemic tissues more rapidly and to a higher level than in the wild-type mice. One role of IL-6 during a Y. enterocolitica infection may be the downmodulation of the inflammatory response. The IL-6(-/-) mice have a more robust T(H)1 T-cell response, as well as hyperinflammatory pathologies. These phenotypes appear to be due to the misregulation of tumor necrosis factor alpha, monocyte chemotactic protein 1, IL-10, transforming growth factor beta1, and gamma interferon in the IL-6(-/-) mouse. These data provide further insight into the intricate cytokine signaling pathways involved in the regulation of inflammatory responses and the control of bacterial infections.
Dube
Peter H
PH
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Handley
Scott A
SA
Lewis
James
J
Miller
Virginia L
VL
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000473:pathology; D014774:Virulence; D015009:Yersinia Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D015008:Yersinia enterocolitica / Q000472:pathogenicity*
D016207:Cytokines; D015850:Interleukin-6