Role of Macrophage Migration Inhibitory Factor in Otitis Media with Effusion in Adults

Abstract

Otitis media with effusion (OME) is one of the most common ear diseases. Bacterial endotoxins and several inflammatory cytokines appear to be involved in the pathogenesis of OME in children; however, little is known of the immunological aspects of the onset of OME in adults. We sought to determine the presence of macrophage migration inhibitory factor (MIF) as well as interleukin 1␤ (IL-1␤), tumor necrosis factor alpha (TNF-␣), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), and endotoxin in middle ear effusions (MEEs) from adult patients with OME. In addition, the levels of MIF in MEEs from adults and children were compared. MEE was obtained from 95 adults and 11 children. The levels of MIF, IL-1␤, TNF-␣, and RANTES were determined by enzyme-linked immunosorbent assay, and the concentrations of endotoxin and total protein were determined by the Endospec assay and bicinchoninic acid assay, respectively. MIF was detected in 97.9% of the MEEs from adults, while endotoxin, IL-1␤, TNF-␣, and RANTES were detected in 96.8, 12.6, 5.3, and 43.9%, respectively. In addition, the level of MIF was significantly higher than those of endotoxin, IL-1␤, and TNF-␣. A positive correlation between the levels of MIF and endotoxin was observed. MIF and endotoxin were detected in 81.8 and 72.7%, respectively, of the MEEs from the children. The level of MIF was significantly higher in the children, and conversely that of endotoxin was significantly higher in the adults. These results suggest that the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults.

Blocking macrophage migration inhibitory factor activity alleviates mouse acute otitis media in vivo

“…In this study, we found that the mRNA and protein levels of MIF were up-regulated in mouse AOM model, which was also observed in the pathogenesis of OM [6,10]. ISO-1 is the most frequently studied MIF small molecule antagonist.…”

“…MIF was originally reported as a cytokine preventing random macrophage migration in tissue with inflammation; however, it has now been reported that MIF has multiple functions, both within and outside of immune system, on pituitary hormone, growth factor, and pro-inflammatory cytokines [5]. Lipopolysaccharides (LPS) from gram-negative bacteria have been shown to be powerful inducers of MIF secretion by macrophages, and autocrine and paracrine signaling of MIF induces the release of tumor necrosis factor (TNF)-α from macrophages in otitis media with effusion (OME) in adults [6]. It has been shown that TNF-αcan modulate the expression of Toll-like receptors (TLR) and is also essential for TLR signaling, including nuclear factor (NF)-κB, via both positive [7] and negative [8] feedback mechanisms.…”

“…Research has also shown that increased concentrations of MIF in middle ear effusion are positively correlated with the levels of LPS, interleukin (IL)-1β and TNF-α in OME of adults [6]. MIF has been considered as an important factor in many inflammatory diseases, such as rheumatoid arthritis, SLE, Wegener’s granulomatosis [11], but its role in mouse AOM has not been fully understood.…”

Th1/Th2 and Regulatory Cytokines in Adults With Otitis Media With Effusion

“…The pathogenesis of mucoid OME has been considered to differ from that of serous OME (3). A small number of reports described the cytokine expression in mucoid MEEs of children with OME (17), whereas only one report described the cytokines in mucoid MEEs of adults with OME (6).…”

“…In addition, allergic mediators, including Th2 cytokines, are considered principally involved in the pathogenesis of OME (3). The lipopolysaccharides present in high percentage in middle ear effusions (MEEs) of adults with OME (6), and IL-12 promotes the secretion of IFN-F, IL-2, IL-8, and granulocytemacrophage colonyYstimulating factor under the stimulation of lipopolysaccharides (7,8).…”