MIF attenuates the suppressive effect of dexamethasone on IL-6 production by nasal polyp

T. Stathas, S.D. Athanassiou, S. Drakouli, E. Giannopoulou, N.S. Mastronikolis, S. Naxakis, A.J. Aletras

Departments of Otorhinolaryngology and Pharmacology Medical School, University of Patras, Patras, Greece. aletras@chemistry.upatras.gr

 

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• Otorhinolaryngology

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the upper airways, that characterized by inflammatory cells infiltration, extracellular matrix accumulation and oedema. Interleukin-6 (IL-6) is a multifunctional cytokine, implicated in various inflammatory conditions, including NP pathogenesis. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory mediator able to antagonize the inhibitory effects of glucocorticoids on the expression of various cytokines and growth factors.
Aim: To investigate the presence of MIF in nasal polyp tissues and the influence of a MIF activity inhibitor on dexamethasone effects on IL-6 production.

PATIENTS AND METHODS: Nasal polyps were resected by functional endoscopic sinus surgery for treatment of chronic sinusitis with polyposis and healthy nasal mucosa was taken during nasal septoplasty-chochoplasty. MIF and IL-6 levels were determined by ELISA. The expression of MIF and IL-6 at the mRNA level was ascertained by RT-PCR.

RESULTS: MIF was detected in all polyp tissue extracts and tissue cultures conditioned media. MIF and IL-6 expression were significantly higher in polyp tissues as compared to normal nasal mucosa tissues. Dexamethasone at concentration 1-100 microM caused a statistically significant dose-dependent suppression of IL-6 production by polyp tissue cultures. Inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of MIF tautomerase activity, significantly enhanced the dexamethasone suppressive effect on IL-6 production.

CONCLUSIONS: MIF, presence in polyp tissue, attenuates the suppressive effect of dexamethasone on the production of IL-6 by this tissue, since the simultaneous use of its inhibitor ISO-1 leads to an enhancement of dexamethasone activity. Therefore, it is reasonable to propose that the utilization of MIF inhibitors together with glucocorticoids in clinical practice may be beneficial in the treatment of NP.

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