Mast Cells as Targets of Pimecrolimus

Abstract

Mast cells, the multi-functional secretory cells, are the pivotal effector cells in immune response, and contribute to the pathogenesis of many diverse diseases, like asthma and mastocytosis, by releasing numerous proinflammatory mediators. Pimecrolimus (SDZ ASM 981) is a derivative of the macrolactam ascomycin and is a member of the calcineurin inhibitor class of immunosuppressors. It inhibits the calcineurin-dependent activation of nuclear factor of activated T cells and the expression of a number of proinflammatory cytokines in turn. Pimecrolimus has high and selective anti-inflammatory activity within the skin, and with much lower potential to affect local and systemic immune responses. Therefore it has been widely used for treatment of various inflammatory skin diseases. It has a cellselective mode of action, and mast cells are its specific target cells. Pimecrolimus inhibits the release of both preformed and de novo synthesized mediators from activated mast cells and inhibits accumulation of mast cells by inducing apoptosis. Several experimental and clinical reports have demonstrated the successful application of pimecrolimus and other calcineurin inhibitors, such as tacrolimus and cyclosporine A, to treat mastocytosis, a spectrum of disorders characterized by mast cell hyperplasia, especially cutaneous mastocytosis. These new findings suggest that pimecrolimus and other calcineurin inhibitors may be a novel and effective therapeutic approach for mast cell-associated diseases such as asthma and mastocytosis.

A web-based appointment system to reduce waiting for outpatients: A retrospective study

“…Reducing outpatient waiting times has been the focus of a large number of studies [1-3] because waiting and treatment times are usually regarded as indicators of service quality [4]. The Patient's Charter of the UK Government sets a series of standards which state that all patients must be seen within thirty minutes of their appointment time [1].…”

Topical pimecrolimus for paediatric cutaneous mastocytosis

“…It acts through blockage of T‐cell activation and inhibition of synthesis of inflammatory cytokines, and has been shown to be effective in the treatment of inflammatory skin diseases . Pimecrolimus has been shown to prevent the release and synthesis of cytokines and proinflammatory mediators from activated mast cells . It reduces the density of cutaneous mast cells through the induction of apoptosis, subsequently diminishing the production and liberation of histamine and other preformed and de novo mast cell mediators .…”

“…Pimecrolimus has been shown to prevent the release and synthesis of cytokines and proinflammatory mediators from activated mast cells . It reduces the density of cutaneous mast cells through the induction of apoptosis, subsequently diminishing the production and liberation of histamine and other preformed and de novo mast cell mediators . Lee et al .…”

“…17,18 Pimecrolimus has been shown to prevent the release and synthesis of cytokines and proinflammatory mediators from activated mast cells. [17][18][19][20] It reduces the density of cutaneous mast cells through the induction of apoptosis, subsequently diminishing the production and liberation of histamine and other preformed and de novo mast cell mediators. 19,20 Lee et al reported an 86-year-old man with telangiectasia macularis eruptiva perstans, a rare form of CM, which was treated with pimecrolimus 1% cream for 2 months with almost complete resolution.…”

Bullous mastocytosis in a 3-month-old infant

“…Topical steroids, photochemotherapy, topical tacrolimus or pimecrolimus, topical miltefosine or intralesional injections of corticosteroids may also be useful. [141516] Second-generation and newer tyrosine kinase inhibitors (e.g. dasatinib and midostaurin [PKC412]) are potential therapeutic options, which might have promising activity in SM cases.…”