Library

Notes: Cetirizine, a H1-receptor antagonist, exerts besides its well-known anti-allergic potential an array of anti-inflammatory activities. In particular epithelial cells activated in the presence of cetirizine showed a reduced ICAM-1 cell surface expression and a diminished release of sICAM-1.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveWe wondered whether cetirizine might influence the release of interleukin-8 (IL-8) from human epithelial cells activated with agonists distinct from histamine.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsWe used the human lung epithelial cell line A549 for our in vitro studies. IL-8 release was determined by IL-8 enzyme immunoassay, the intracellular staining for IL-8 and NF-kB was analysed by FACS analysis and IL-8 mRNA steady state level was studied by Northern blot analysis. Confluent epithelial cell monolayer were pre-incubated with cetirizine (0.01 −1.0 μmol/L) for 30 min and afterwards activated with pro-inflammatory cytokines (TNF-α IL-1β, IL-6, IFN-γ) or different agonists (PMA, NaF, respiratory syncytial virus [RSV]) for 24 h.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsEpithelial cells stimulated with TNF-α IL-1β, PMA and RSV, respectively, showed a significantly increased release of IL-8. Pre-incubation with cetirizine diminished the IL-8 release from cells activated with TNF-α or PMA in a significant manner. The reduced IL-8 release coincided with a diminished percentage of cells expressing IL-8. Northern blot analysis revealed a reduced steady state level of IL-8 mRNA in cells pretreated with cetirizine and stimulated with TNF-α. Furthermore, a decreased amount of accessible DNA-binding sites of the nuclear factor kappa B (NF-kB) was determined by FACS analysis.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionsThese results suggest that cetirizine reduced the release of IL-8 from A549 cells stimulated with PMA and TNF-α, respectively, by lowering IL-8 gene expression. Therefore, cetirizine might exert anti-inflammatory effects beyond its H1-receptor antagonistic activity in the course of inflammatory respiratory tract disorders such as bronchial asthma and allergic rhinitis.

Notes: 26 different compounds have been investigated experimentally for their sensitizing capacity in guinea pigs. 19 of these occur in propolis as well as in poplar bud exudates, and 14 of them are also found in balsam of Peru. 4 caffeates and benzyl isoferulate were found to be strong Sensitizers. 7 compounds were moderate, and 13 compounds showed only weak sensitizing potency. Methyl cinnamate was negative. Patch tests in 11 propolis-sensitive patients once more revealed 3-methyi-2-butenyl caffeate and phenylethyl caffeate as the major sensitizers. In addition to the 8 compounds already known to occur in propolis as well as in balsam of Peru, we detected 5 further substances that both materials have in common. Among these, benzyl isoferulate is considered a noteworthy sensitizer. Coniferyl benzoate, which was shown to be a moderate sensitizer, is present in fresh samples of balsam of Peru, while in propolis it has been detected only once so far. The flavonoid aglycones occurring in poplar bud exudates, and hence also in propolis, are weak sensitizers which play only a minor role m propolis hypersensitivity.

Notes: Experimental and chemical investigations revealed that common ivy (Hedera helix susp. Helix) contains 3 compounds which are powerful irritants and moderate sensitizers. Only 2 of these constituents, falcarinol and didehydrofalcarinol, are present in the plant during the whole year. Besides Panax ginseng and Schefflera arboricala, this is the third species of the Araliaceae in which these polyacetylenic sensitizers have been found. Falcarinol and didehydrofalcarinol also occur in Hedera helix subsp. canariensis. 4 patients have been patch tested. Even in low concentrations (0.03%). the main allergen falcarinol elicited strong reactions in all of them. One of the authors became sensitized during the investigations.

Notes: Irritancy of daffodil flowers and bulbs was assessed using various fresh plant preparations, solvent extracts and some of the known Amaryllidaceae alkaloids on guinea pigs. Sensitization was also carried out on guinea pigs using these plant preparations. solvent extracts and 7 fractions obtained after preparative chromatography of the bulb ether extract. Only 1 fraction, containing 2 alkaloids, was capable of inducing delayed hypersensitivity in the animals: the sensitivity achieved, however, was weak. The substances were identified as masonin and homolycorin, which acted as elicitors. but masonin may also be a sensitizer. While homolycorin is a known daffodil constituent, masonin has not been found previously in Narcissus pseudonarcissus. 3 other alkaloids as well as chelidonic acid and isorhamnetin were non-elicitors in the sensitized guinea pigs.

Notes: An eosinophil chemotactic factor (ECF) of low molecular weight can be generated and released from human polymorphonuclear neutrophils by the calcium ionophore, phagocytosis of zymosan particles, arachidonic acid, and phospholipase A2. Since the activation of cells by the ionophore and during the phagocytic event leads to phospholipid turnover, with the subsequent generation of arachidonic acid, it is reasonable that phospholipase A2 represents the common link for ECF production. The kinetics of ECF release by phospholipase A2 is similar to the pattern observed with the various stimuli. After a rapid rise in activity a decline occurred at later times of secretion, suggesting a mechanism of inactivation. During subcellular fractionation of cells an ECF-generating component was enriched in the 200,000 g supernatant fraction, which represents the cytosol. Addition of arachidonic acid or phospholipase A2 induced ECF generation. On gel filtration analysis the ECF-generating component revealed a molecular weight of about 80,000 daltons. It is suggested that this component represents a lipoxygenase.