Chronic rhinosinusitis (CRS) is defined as an inflammatory condition involving the paranasal sinuses and the lining of the nasal passages that persists longer than 12 weeks. It is one of the most common chronic diseases today, affecting up to 15% of the adult population in the Western world with a dramatic increase in prevalence. One hallmark of chronic inflammation in CRS is the predominance of eosinophils and T lymphocytes in the inflamed tissue. We pursued the hypothesis that the blockage of the paranasal sinuses induces hypoxic conditions, which subsequently lead to the induction of chemotactic activity, attracting inflammatory cells. To this end, we established an in vitro model by showing that hypoxia is able to induce the release of chemokines in nasal epithelial cells. Furthermore, we show that this induction leads to the migration of eosinophils and neutrophils. Finally, we demonstrated the applicability of this in vitro model by showing its sensitivity to the glucocorticoid dexamethasone, which is used in the clinical situation. These results suggest that this nasal epithelial cell culture model may allow the evaluation of novel anti-inflammatory compounds for the treatment of CRS directly on the relevant target cells in vitro. This approach may result in replacing and refining animal experimentation in the screening of new therapeutics for CRS.
New concepts of the horny layer as a metabolically active part of the epidermal permeability barrier elicited a re-evaluation of conventional mechanisms of occupational skin protection. Both skin protection products and noxae must penetrate the horny layer of the skin to be effective. The isolated perfused bovine udder skin (BUS) model reflects the natural penetration pattern; hence skin irritation, penetration and absorption can be investigated simultaneously. Using whole skin biopsies the degree of irritation in untreated (control), treated and pre-treated skin is measured by assessing the irritancy (PGE2-concentration) and cytotoxicity (MTT assay) after the exposure period of 0.5 h, 1.0 h and 5.0 h. Two types of skin protection studies were reported. One was a laboratory study using the water-soluble sodiumlaurylsulphate (10%, 15%) as noxa. The other study was initiated by a severely skin irritating water-soluble coolant (approx. 5%). This well documented case occurred in a metal working plant. In both studies different degrees of protective potential against the model noxae SLS and the coolant could be observed.