A LOCAL LYMPH-NODE ASSAY TO ANALYZE IMMUNOSUPPRESSIVE EFFECTS OF TOPICALLY APPLIED DRUGS

Topical glucocorticosteroids represent the mainstay of antiinflammator y therapy in the treatment of inflammatory skin diseases. Their clinic al use, however, is limited by local and systemic side-effects. Thus, in dermatopharmacology there is a large demand for alternative non-ste roidal antiinflammatories. Other than transplantation models, most of the frequently used in vivo test systems for assessment of drug-induce d immunosuppression measure changes in inflammatory skin responses by means of skin erythema and edema after challenge of sensitized animals . The aim of this study was to develop an alternative mouse model to d etect and analyse immunosuppressive effects of topically applied drugs . On the basis of a modified local lymph node assay, we analysed effec ts of topical hydrocortisone, dexamethasone, mometasone furoate and FK 506 (tacrolimus) during the induction phase of contact hypersensitivit y. On 4 consecutive days, NMRI mice were treated on the dorsal surface s of both ears with increasing concentrations of test compound. During the last 3 days, the mice received in addition the contact sensitizer , oxazolone (1%). On day 5, draining auricular lymph nodes were remove d in order to assess lymph node cell counts and perform flow cytometri c analysis of lymph node cell subpopulations (CD4(+)/CD25(+), Ia(+)/CD 69(+), Ia(+)/B220(+)). All test compounds proved to exert significant immunosuppressive effects after topical application, but showed differ ences in their immunomodulatory potential. In conclusion; the local ly mph node assay serves as an appropriate model to characterize immunosu ppressive effects of topically applied drugs by measuring immunologica lly relevant end-points. (C) 1997 Elsevier Science B.V.