Topical tacrolimus for the treatment of inflammatory skin diseases

Abstract

Chronic inflammatory skin disorders, such as atopic eczema, can cause considerable impairment of life quality. Their treatment is mainly driven by systemic or topical glucocorticosteroids which have the risk of many side effects. Recently, immunosuppressive macrolides which act via the inhibition of cytokine expression in T-lymphocytes have been shown to exert good therapeutic potency in inflammatory skin disorders. Cyclosporin, widely used in transplantation medicine, is also effective in psoriasis and atopic eczema but is not suitable for topical treatment. Tacrolimus (FK506) has been found to be 10-100 times more potent than cyclosporin and to penetrate skin much better due to a lower molecular weight. Initial clinical investigations have shown efficacy of topical tacrolimus in patients with atopic eczema. Large multi-centre studies have proven that long-term therapy with 0.03% and 0.1% tacrolimus ointment reveals effectiveness and safety both in adults and in children with severe atopic eczema. A burning sensation at the site of application is the most frequently observed local side effect. Relevant systemic adverse events were not detected. In Japan and the US, the drug is already licensed for the treatment of atopic eczema. The European admission for the pharmaceutical market is expected in the year 2002. Tacrolimus represents a milestone in topical therapy of inflammatory skin disorders which has so far been dominated by corticosteroid formulations and gives hope for the development of further topical immunosuppressive agents of its class in the future.

Topical Application of FK506 (Tacrolimus) Ointment Inhibits Mite Antigen-Induced Dermatitis by Local Action in NC/Nga Mice

“…Topical application of FK506 ointment exerts good therapeutic efficacy in atopic eczema [9]. FK506 ointment penetrates through skin [10], and clinical studies have shown that FK506 reduces cytokine production and infiltration of T helper (Th) cells in the skin of AD patients [11]. Treatment with FK506 ointment in the conventional NC/Nga model also produces a decreased level of clinical signs and the reduction of Th2 cytokines in the skin [12].…”

Steroidaggravierte Rosazea

“…Es bewirkt über eine Hemmung der Calcium/Calmodulin-abhängige Phosphatase Calcineurin eine Reduktion der Zytokinausschüttung (IFN-γ, IL-2, IL-4, IL-10) und damit eine Blockade der T-Zellaktivität [13]. Wäh-rend Ciclosporin die Haut nur schlecht durchdringt, weisen topisches Pimecrolimus und Tacrolimus eine gute Penetrationsfähigkeit auf [2,4]. Pimecrolimus ist in Deutschland zur Behandlung der atopischen Dermatitis ab dem 2.…”

Topische Immunmodulation in der Dermatologie

“…Calcineurin-Inhibitoren), was zur Blockade der T-Zell-Aktivierung und der Zytokinausschüttung führt. Calcineurin-Inhibitoren hemmen insbesondere die Produktion der Th 1 -Zytokine IFN-γ, IL-2 sowie der Th 2 -Zytokine IL-4 und IL-10 [3]. Während Ciclosporin die Haut nur schlecht penetriert,wurden topisches Tacrolimus und Pimecrolimus vor kurzem in die dermatologische Therapie eingeführt.…”

“…Tacrolimus ist lipophil und hemmt den "second messenger" Calcineurin, was zur Hemmung der Transkription proinflammatorischer Zytokine wie Interleukin-2 und Interferon-γ führt [3].Die Klasse der Calcineurin-Inhibitoren reduziert die Antigenprozessierung und die T-Zell-Aktivierung. Daneben hat Tacrolimus hemmende Wirkung auf Mastzellen und basophile Granulozyten und die Zytokine IL-3, IL-8, IL-13, and GM-CSF.…”