title: Effects of topical treatment with budesonide on parameters for epidermal proliferation, keratinization and inflammation in psoriasis.
abstract: Corticosteroids are important in the treatment of inflammatory dermatoses, such as psoriasis. They have anti-inflammatory, anti-proliferative and immunosuppressive effects. In this study, the effect of budesonide on proliferation, inflammatory cells and cytokines in psoriasis was investigated. In order to elucidate the time course of the different effects of corticosteroid treatment in psoriasis, six patients were treated for 3 weeks with budesonide 0.025% ointment (Preferid), and biopsies were studied immunohistochemically, before treatment and after 1 and 3 weeks of treatment. Clinical scores together with staining with antibodies indicating proliferation, keratin 16, keratin 10, T-lymphocytes, monocytes, polymorphonuclear leukocytes, Langerhans cells, interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) were performed. 'Psoriasis area' and 'severity index' (PASI) scores were significantly reduced after 1 week and 3 weeks of treatment. Epidermal hyperproliferation (Ki-67 binding) and suprabasal keratin 16 (Ks8.12) expression decreased within 1 week, while keratin 10 (RKSE60) expression did not change. Five out of 6 patients showed cytokine levels (IL-1alpha, IL-6, IL-8, and TNF-alpha; detected immunohistochemically) in the normal range, while 1 patient had highly increased cytokine levels. In this patient, cytokine levels decreased during treatment. In 4 patients, showing high dermal ICAM-1 expression before treatment, a consistent reduction of ICAM-1 on endothelial cells was observed. The inflammatory infiltrate (T-lymphocytes (T11), monocytes/macrophages (WT14), polymorphonuclear leukocytes (PMN, anti-elastase)) was reduced to some extent after 3 weeks. The number of Langerhans cells (OKT6) did not change. These results indicate that the psoriatic lesions, although clinically comparable, show interindividual differences in cytokine expression. Corticosteroid treatment for 1-3 weeks improves clinical scores and hyperproliferation. Cytokine levels are reduced during steroid treatment in the patient who showed high levels before treatment. To suppress the infiltrate entirely, longer steroid treatment is probably necessary. This may explain the relapse seen after short term corticosteroid therapy.
authors.affiliation: Department of Dermatology, University Hospital Nijmegen, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: de Jong
authors.forename: C M
authors.initials: CM
authors.lastname: Ferrier
authors.forename: A
authors.initials: A
authors.lastname: de Zwart
authors.forename: P J
authors.initials: PJ
authors.lastname: Wauben-Penris
authors.forename: C
authors.initials: C
authors.lastname: Korstanje
authors.forename: P C
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers; D019819:Budesonide; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011282:Pregnenediones / Q000008:administration & dosage*; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D011282:Pregnenediones; D019819:Budesonide; D007633:Keratins