A new model of local inflammation has been developed: intradermal zymosan-induced mouse ear edema. The symptoms of inflammation induced by injecting zymosan into one of the ears were followed up for 72 h. The ear edema and the local accumulation of polymorphonuclear leukocytes' (PMN) marker enzyme, myeloperoxidase (MPO), were determined. Edema peaked at 4-6 h, while MPO activity peaked at 24 h after zymosan application. The correlation between inflammatory response and concentration of zymosan was also tested. Of the various concentrations tested, 1% suspension has been found optimal. Anti-inflammatory drugs and mediator antagonists were examined in order to establish the selectivity and sensitivity of the assay. A glucocorticoid (dexamethasone), two cyclooxygenase inhibitors (indomethacin, piroxicam) and an interleukin-1 (IL-1) release inhibitor (IX 207-887, Sandoz) all reduced edema and MPO activity as well. However, a lipoxygenase inhibitor (phenidone), a serotonin receptor antagonist (methysergide) and H1 and H2 receptor antagonists (clemastine and cimetidine, respectively) all failed to inhibit the reaction.

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Microdialysis (MD) techniques were first applied in the early 1960s. The fields of their application comprised probe implantation into the central nervous system (CNS) at the beginning, and then expanded to almost every organ summarized in this article. After its early experimental applications MD became an important tool in the human pharmacokinetic/pharmacodynamic (PK/PD) studies as well. This monitoring technique is capable for investigation of local unbound concentrations of both endogenous and exogenous compounds in the interstitial fluid. The review shows examples for the role of MD in pharmacodynamic studies and for its use in tissue distribution and drug-transporter interaction studies. Determination of test substances in the dialysate samples needs sensitive bioanalytical methods. The main analytical techniques coupled with MD are summarized under the subtitle "Target molecules". New trend in the application of MD is the determination of large molecular entities in the extracellular fluid of target tissues. This approach greatly helps in the discovery of new pathophysiological pathways and identification of new therapeutic intervention strategies for several disorders. Finally, the article gives an overview on the complementary techniques (positron emission tomography, magnetic resonance spectroscopy and open flow microperfusion), and presents their advantages and limitations versus to in vivo MD. In summary, MD techniques have a wide variety of the fields of application. There are several new approaches using this methodology. The relatively low price and the importance of the information gained on the pharmacologically active form of the test articles at the site of interest guarantees a significant position of this technique in the preclinical and clinical research.

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The aim of the present study was to examine whether interleukin-1 (IL-1) production is involved in the pathology of inflammation induced by zymosan in the air-pouch of mice. For this reason the IL-1 alpha level was determined in the air-pouch exudate by specific ELISA kit 4, 24, 48 h and 4-8 days after zymosan injection into preformed subcutaneous air-pouches in mice. Concurrently, some conventional parameters such as volume of exudate, its protein content and the total leukocyte count were also measured. The IL-1 alpha level reached its maximum 24 h after zymosan administration and remained elevated throughout the 8-day observation period. Exudation, accumulation of leukocytes and protein also were maximal on day 8. The effects of some anti-inflammatory agents have also been examined. Orally administered dexamethasone induced a dose-dependent reduction in IL-1 alpha, whereas indomethacin and IX 207-887, an IL-1-release inhibitor, failed to reduce the IL-1 alpha content in this model.