Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment

Simon, Dagmar; Vassina, Ekatherina; Yousefi, Shída; Braathen, Lasse R.; Simon, Hans‐Uwe

doi:10.1111/j.1398-9995.2005.00798.x

Cited by 47 publications

(40 citation statements)

References 39 publications

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“…On the other hand, the consistently lower sensitivity of primary activated, PBMC-derived T cells towards pimecrolimus indicates a lower ability to interfere with de novo T cell responses to antigen. This assumption is supported by a recent study showing that topical pimecrolimus applied for 3 weeks reduced the inflammatory cell infiltrate and T cell cytokine expression in the dermis, whereas it did not reduce the capacity of PBMC-derived T cells to proliferate or secrete cytokines following PHA stimulation ex vivo [23]. This picture fits with the differential profile of systemically applied pimecrolimus and tacrolimus shown in CHS.…”

Section: Discussionsupporting

confidence: 73%

Differential Inhibition of Primary versus Preactivated T Cells by Pimecrolimus but Not by Tacrolimus in vitro

Kalthoff

Winiski

Fichtinger

et al. 2006

Int Arch Allergy Immunol

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Background: Recent studies in murine models of allergic contact dermatitis have shown that systemic treatment with pimecrolimus in contrast to tacrolimus did not inhibit the sensitization phase, whereas both compounds equivalently suppressed the inflammatory response in sensitized animals. This finding indicated a differential sensitivity of antigen-naïve and primed T cells towards pimecrolimus and tacrolimus. Methods: T cells obtained from healthy and allergic donors were subjected to primary and secondary stimulation by allogeneic or staphylococcal superantigen-presenting dendritic cells (DC). Human skin-derived, allergen-specific T cell clones from an atopic dermatitis patient were activated by anti-CD3 antibodies or by specific allergen-presenting DC. The inhibition of T cell proliferation and cytokine release by graded doses of calcineurin inhibitors was evaluated. Results: Primary stimulation of T cells was inhibited by pimecrolimus with an approximately 8-fold lower potency as compared with tacrolimus. In contrast, the secondary response of ex vivo expanded T cells activated by allogeneic or staphylococcal superantigen-presenting DC was inhibited by both compounds with equivalent potency. Likewise, both drugs showed very similar potency to inhibit the proliferation and cytokine synthesis from antigen- stimulated T cell clones and the induction of cytokines in Jurkat T cells. Conclusion: These data indicate that pimecrolimus has a selectivity for antigen-primed memory T cells not seen with tacrolimus.

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Section: Discussionsupporting

confidence: 73%

Differential Inhibition of Primary versus Preactivated T Cells by Pimecrolimus but Not by Tacrolimus in vitro

Kalthoff

Winiski

Fichtinger

et al. 2006

Int Arch Allergy Immunol

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“…Topical pimecrolimus has been shown to prevent the DC-mediated proliferation of T cells in an in vitro model of recurrent antigenic stimulation that mimics the recurrent allergic stimulation in the skin of AD patients [45]. This mechanism of action seems to be operative in vivo as evidenced by the reduced synthesis of IL-5, IL-10 and IL-13 receptor (T helper type 2 cytokine profile) in the T lymphocytes following application of pimecrolimus cream 1% [20]. In addition, treatment of acute AD lesions with pimecrolimus cream 1% leads to an apoptosis-induced depletion of pathological T cells in the skin without interfering with the viability of LCs [19].…”

Section: Discussionmentioning

confidence: 99%

“…Both topical corticosteroids and the two calcineurin inhibitors reduce the inflammatory infiltrate and the release of proinflammatory cytokines in the lesional skin [16,17,18,19,20], but the latter exhibit a more selective mode of action than topical corticosteroids [19,21,22]. Because of the concerns about potential side effects associated with prolonged treatment [23], topical corticosteroids are generally not used as long-term therapy especially on nonlesional skin or during remission [2,23].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Cytological Effects of Pimecrolimus Cream 1% after Resolution of Active Atopic Dermatitis Lesions by Topical Corticosteroids: A Randomized Controlled Trial

Bangert

Strober²,

Cork³

et al. 2010

Dermatology

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Background: Topical pimecrolimus may maintain remissions of atopic dermatitis (AD) by inhibiting subclinical inflammation. Objective: To evaluate clinical and cytological effects of pimecrolimus in topical corticosteroid-treated and resolved AD lesions. Methods: Patients (n = 67) with resolved AD lesions were randomized to 3-week double-blind treatment with either pimecrolimus cream 1% or vehicle cream. Outcome measures were reduction in Eczema Area and Severity Index (EASI) and number of leukocytes in skin biopsies in all randomized patients who were evaluable at the end of study. Results: The proportion of patients with a localized EASI <2 at the end of study was higher with pimecrolimus cream 1% than with vehicle cream (73.5 vs. 39.4%, respectively). There was a significant decrease in the number of infiltrating CD45+ cells in pimecrolimus cream 1% compared with placebo cream (–88.2 vs. 43.2 cells/mm², respectively, p = 0.047) and a slight but nonsignificant reduction in the number of dermal dendritic cells, Langerhans cells, T cells and macrophages with pimecrolimus versus vehicle cream. Limitations: This was an exploratory study. Conclusion: Topical pimecrolimus was effective at maintaining betamethasone-17α-valerate-induced AD remission by inhibiting recurrences of the inflammatory infiltrate in the skin.

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“…В результате происходит ингибирование транскрипции генов ключевых провоспа-лительных цитокинов -ИЛ2, 3, 4, 8, 10 и ФНОα, ИФγ. Такролимус дает также иммуномодулирующий эффект [7,68,110,113,137,143].…”

Section: лечениеunclassified

Clinical and laboratory rationale for photodynamic therapy in patients with severe complicated oral lichen planus

2015

Stomat.

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Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment

Abstract: Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.

Cited by 47 publications

References 39 publications

Differential Inhibition of Primary versus Preactivated T Cells by Pimecrolimus but Not by Tacrolimus in vitro

Differential Inhibition of Primary versus Preactivated T Cells by Pimecrolimus but Not by Tacrolimus in vitro

Clinical and Cytological Effects of Pimecrolimus Cream 1% after Resolution of Active Atopic Dermatitis Lesions by Topical Corticosteroids: A Randomized Controlled Trial

Clinical and laboratory rationale for photodynamic therapy in patients with severe complicated oral lichen planus

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