title: Effects of dexamethasone on macrophage migration inhibitory factor production in sepsis.
abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a major role in the pathogenesis of sepsis. Some studies have indicated that glucocorticoids increase MIF production in physiological conditions. The goal of this study was to determine whether glucocorticoid treatment also upregulates MIF production in sepsis. Male NMRI mice (6-10 weeks old) underwent laparotomy, proximal ligation of the cecum, and double perforation with a 19-gauge needle (cecal ligation and puncture). Mice were randomly treated with saline (control) or dexamethasone at doses of 0.1, 1, or 10 mg/kg ip. At 6 or 18 h postoperatively, 10 mice per group were euthanized; and blood, peritoneal fluid, liver, lung, kidney, and heart tissue samples were retrieved. MIF, IL-6, TNF-alpha, and IL-10 were measured by enzyme-linked immunosorbent assay. Sepsis induced by cecal ligation and puncture produced a marked increase in MIF and cytokine levels in plasma and peritoneal fluid. Treatment with dexamethasone 10 mg/kg decreased MIF levels in plasma after 18 h, but there was no effect of dexamethasone on MIF production locally in the peritoneal cavity or in the liver, lungs, heart, or kidneys. We conclude that glucocorticoid treatment does not upregulate MIF production in sepsis.
authors.affiliation: Department of Intensive Care, Erasme Hospital.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bruhn
authors.forename: Colin
authors.initials: C
authors.lastname: Verdant
authors.forename: Vincent
authors.initials: V
authors.lastname: Vercruysse
authors.forename: Fuhong
authors.initials: F
authors.lastname: Su
authors.forename: Bernard
authors.initials: B
authors.lastname: Vray
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010533:Peritoneal Lavage; D010538:Peritonitis / Q000188:drug therapy / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone