gms | German Medical Science

Introduction: Mucus overproduction is commonly found in allergic induced inflammation of the upper airway, mainly driven by Th-2-cytokines IL-4, IL-9 and IL-13. In the past, studies were usuallydone by using an animal or cell line model.

We sought to examine the simulation of an allergic induced inflammation by Th-2-cytokines and its inhibition by dexamethasone in an ex vivo model of explanted human airway mucosa.

Methods: Mucosa of the upper airway, which was collected in conchotomies (n=9), was cultivated over a period of 24h (explant model) and stimulated with recombinant human IL-4, IL-9 and IL-13 (50ng/ml). Dexamethasone was added in increasing concentrations (4, 40, and 400µM) to stimulated as well as to non-stimulated probes. As a comparing model, mucoepidermoid cells (Calu-3) were treated the same way.

The mucus overproduction was quantified via PAS staining using the PAS-Score (0= no cell positive, to 4=all cells positive) and via the expression of MUC5AC mRNA in Calu-3 cells using Real time PCR.

Results: In the explant model of human mucosa, IL-4, IL-9, and IL-13 induced a significant increase of mucus (p< 0,05). Dexamethasone alone had no significant influence on the mucus production. In contrast to this, the mucodermoid cell culture model (Calu-3) showed no increase of MUC5AC mRNA expression after stimulation with Th-2-cytokines. Depending on the concentration, dexamethasone reduced significantly the IL-4 and IL-13 induced mucus overproduction but failed in IL-9 driven stimulation.

Discussion: Allergic inflammation can be reproduced in the ex vivo explant model of human nasal mucosa. According to the clinically established fact, the Th-2-cytokine driven stimulation as well as the inhibition by dexamethasone can be imitated. In contrast, the mucodermoid cell culture model (Calu-3) does not seem to be suitable. It might be postulated that beside epithelic cells inflammatoric cells are required for establishing an allergic inflammatoric process.

The effect of cortisone on allergic induced mucus production is clinically well known and is evident in the significant reduction regarding to IL-4 and IL-13. The failure of cortisone in IL-9 driven inflammation stays unclear and needs further observation.

The explant model of human mucosa of the upper airway is suitable for a realistic simulation of allergic induced mucus overproduction. Potential drugs could be tested in a save, effective and economic manner.