title: Macrophage migration inhibitory factor (MIF) in meningococcal septic shock and experimental human endotoxemia.
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.
authors: Department of General Internal Medicine, The Nijmegen University Centre for Infectious Diseases, Nijmegen, the Netherlands. t.sprong@aig.umcn.nl
authors: Tom
authors: T
authors: Sprong
authors: Peter
authors: P
authors: Pickkers
authors: Anneke
authors: A
authors: Geurts-Moespot
authors: Johanna
authors: J
authors: van der Ven-Jongekrijg
authors: Chris
authors: C
authors: Neeleman
authors: Marlies
authors: M
authors: Knaup
authors: Didier
authors: D
authors: Leroy
authors: Thierry
authors: T
authors: Calandra
authors: Jos W M
authors: JW
authors: van der Meer
authors: Fred
authors: F
authors: Sweep
authors: Marcel
authors: M
authors: van Deuren
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008589:Meningococcal Infections / Q000097:blood* / Q000382:microbiology / Q000473:pathology; D009345:Neisseria meningitidis / Q000254:growth & development; D012772:Shock, Septic / Q000097:blood* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D018664:Interleukin-12