Elevated Plasma Concentrations of Interferon (IFN)–γ and the IFN‐γ–Inducing Cytokines Interleukin (IL)–18, IL‐12, and IL‐15 in Severe Melioidosis
F. N. Lauw,Andrew J. H. Simpson,Andrew J. H. Simpson,Jan M. Prins,M. D. Smith,M. D. Smith,M. Kurimoto,S. J. H. Van Deventer,Peter Speelman,W. Chaowagul,N J White,N J White,T. van der Poll +12 more
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Data suggest that during gram-negative sepsis, IFN-gamma production is controlled at least in part by endogenous IL-18, IL-12, and IL-15.Abstract:
Interferon (IFN)-gamma plays an important role in the pathogenesis of sepsis. Production of IFN-gamma is stimulated by synergistic effects of interleukin (IL)-18, IL-12, and IL-15. To investigate the regulation of IFN-gamma production during severe gram-negative infection, the plasma concentrations of IFN-gamma, IL-18, IL-12, and IL-15 were measured in 83 patients with suspected melioidosis. The diagnosis was confirmed in 62 patients, 31 of whom had blood cultures positive for Burkholderia pseudomallei, of whom 12 died. Compared with healthy controls, patients had elevated levels of IFN-gamma, IL-18, IL-12p40, and IL-15 on admission, with significantly higher levels in blood culture-positive patients, and these levels remained elevated during the 72-h study period. In whole blood stimulated with heat-killed B. pseudomallei, anti-IL-12 had a stronger inhibitory effect than anti-IL-18 and anti-IL-15 on IFN-gamma production. This effect of anti-IL-12 was further enhanced by anti-IL-18. These data suggest that during gram-negative sepsis, IFN-gamma production is controlled at least in part by endogenous IL-18, IL-12, and IL-15.read more
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Melioidosis: Epidemiology, Pathophysiology, and Management
TL;DR: Melioidosis is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans, and the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease.
Journal ArticleDOI
Interleukin 15: biology and relevance to human disease
TL;DR: The cloning of interleukin (IL)-15 and IL-2 have similar biologic properties in vitro, consistent with their shared receptor (R) signaling components (IL-2/15Rβγc).
Journal ArticleDOI
Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei
W. Joost Wiersinga,Tom van der Poll,Nicholas J. White,Nicholas J. White,Nicholas P. J. Day,Nicholas P. J. Day,Sharon J. Peacock,Sharon J. Peacock +7 more
TL;DR: Prevention of disease and a reduction in mortality and the rate of relapse are priority areas for future research efforts, and how the disease is acquired and the host–pathogen interactions involved will underpin these efforts are presented.
Journal ArticleDOI
Bystander activation of CD8+ T cells contributes to the rapid production of IFN-gamma in response to bacterial pathogens.
TL;DR: The preferential activation of NK cells and CD8+ T Cells, rather than CD4+ T cells, was also observed in response to Listeria monocytogenes or a combination of IL-12 and IL-18 both in vitro and in vivo.
Journal ArticleDOI
Interleukin-18 and host defense against infection.
TL;DR: Interferon (IFN)-gamma-inducing factor appears to be a viable clinical target to combat the pathologic consequences of sepsis via IFN-gamma mechanisms.
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