Macrophage migration inhibitory factor (MIF) in meningococcal septic shock and experimental human endotoxemia
Tom Sprong1, Peter Pickkers, Anneke Geurts-Moespot
1Department of General Internal Medicine, The Nijmegen University Centre for Infectious Diseases, Nijmegen, the Netherlands. t.sprong@aig.umcn.nl
Abstract:
Macrophage migration inhibitory factor (MIF) is a mediator of innate immunity and important in the pathogenesis of septic shock. Lipopolysaccharide (LPS) and tumor necrosis factor (TNF) alpha are reported to be inducers of MIF. We studied MIF and cytokines in vivo in patients with meningococcal disease, in human experimental endotoxemia, and in whole blood cultures using a newly developed sensitive and specific enzyme-linked immunosorbent assay. Twenty patients with meningococcal disease were investigated. For the human endotoxemia model, 8 healthy volunteers were intravenously injected with 2 ng/kg Escherichia coli LPS. Whole blood from healthy volunteers was incubated with LPS or heat-killed meningococci. Macrophage migration inhibitory factor concentration in blood was increased during meningococcal disease and highest in the patients presenting with shock compared with patients without shock. Plasma concentration of MIF correlated with disease severity, the presence of shock and with the cytokines interleukin (IL) 1beta, IL-10, IL-12, and vascular endothelial growth factor, but not with TNF-alpha. MIF was not detected in blood in experimental endotoxemia, nor after stimulation of whole blood with LPS or meningococci, although high levels of TNF-alpha were seen in both models. In conclusion, MIF is increased in patients with meningococcal disease and highest in the presence of shock. Macrophage migration inhibitory factor cannot be detected in a human endotoxemia model and is not produced by whole blood cells incubated with LPS or meningococci.
Insights
Macrophage migration inhibitory factor (MIF) is elevated in meningococcal disease, particularly in shock patients. MIF levels did not increase in experimental endotoxemia models, suggesting a complex role in sepsis.
Area of Science:
- Immunology
- Infectious Diseases
- Critical Care Medicine
Background:
- Macrophage migration inhibitory factor (MIF) is a key mediator in innate immunity and septic shock pathogenesis.
- Lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α) are implicated as MIF inducers.
Purpose of the Study:
- To investigate MIF and cytokine levels in meningococcal disease and experimental endotoxemia.
- To explore MIF production in whole blood cultures stimulated with LPS or meningococci.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) used to quantify MIF and cytokines.
- Study included 20 patients with meningococcal disease and 8 healthy volunteers in an experimental endotoxemia model.
- Whole blood cultures were stimulated with LPS or heat-killed meningococci.
Main Results:
- MIF concentrations were increased in meningococcal disease patients, highest in those with shock.
- Plasma MIF correlated with disease severity, shock, and cytokines IL-1β, IL-10, IL-12, and VEGF, but not TNF-α.
- MIF was undetectable in experimental endotoxemia and in vitro stimulated whole blood cultures, despite elevated TNF-α.
Conclusions:
- MIF is upregulated in meningococcal disease, especially in shock.
- MIF is not detected in human endotoxemia models or in whole blood stimulated with LPS/meningococci.
- Findings suggest MIF's role in meningococcal disease pathogenesis may differ from LPS-induced responses.
