Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.
Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS). We show in alveolar cells from patients with ARDS that MIF augments pro-inflammatory cytokine secretion (TNF alpha and IL-8), anti-MIF significantly attenuates TNF alpha and IL-8 secretion and MIF overrides, in a concentration-related fashion, the anti-inflammatory effects of glucocorticoids. These findings suggest that MIF may act as a mediator sustaining the pulmonary inflammatory response in ARDS and that an anti-MIF strategy may represent a novel therapeutic approach in inflammatory diseases such as ARDS.
Donnelly
S C
SC
Rayne Laboratory, Respiratory Medicine Unit, University of Edinburgh, Scotland.
Haslett
C
C
Reid
P T
PT
Grant
I S
IS
Wallace
W A
WA
Metz
C N
CN
Bruce
L J
LJ
Bucala
R
R
D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis* / Q000502:physiology; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha