Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis

Schuller, Erich; Oppel, Tilmann; Bornhövd, Elke; Wetzel, Stefanie; Wollenberg, Andreas

doi:10.1016/j.jaci.2004.03.021

Cited by 56 publications

(43 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results are in line with the recently described reduction in CD1a+/CD11b+ cells after tacrolimus treatment in AE [17]. Interestingly, CD4+ cells were more prominent in pimecrolimus-pretreated skin while CD8+ cells – already being sparse – remained unchanged.…”

Section: Discussionsupporting

confidence: 91%

Modulation of Atopy Patch Test and Skin Prick Test by Pretreatment with 1% Pimecrolimus Cream

Weissenbacher

Traidl‐Hoffmann

Eyerich

et al. 2006

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: In a subgroup of patients with atopic eczema (AE), aeroallergens are relevant eliciting factors. The atopy patch test (APT) was proposed as inflammation model for AE. Objective: It was the aim of this study to investigate the effect of pretreatment with 1% pimecrolimus cream (Elidel^®) on the APT and skin prick test (SPT). Methods: In a randomized, controlled, double-blind study, 20 patients with AE and positive SPT and APT screening reaction to house dust mite Dermatophagoides pteronyssinus, cat dander, grass or birch pollen were enrolled (age 20 ± 11 years, 55% males). For 2 weeks, patients twice daily applied pimecrolimus and vehicle control to marked fields on their backs and forearms. Then, APT was performed (200 index of reactivity/g extracts in petrolatum; Stallergènes, France) on both fields on the back and SPT was performed on the pretreated forearms. Results: Including only patients with different readings (n = 13), stronger APT suppression of at least 1 ETFAD (European Task Force on Atopic Dermatitis) grade in the pimecrolimus area versus intraindividual control was observed in 10 of these patients after 48 and 72 h (p < 0.05; 90% CI 50.5–93.4). Including all 20 subjects, the analysis still showed a borderline significance compared with the vehicle (p = 0.0564). SPT with histamine and aeroallergens showed a median 7.5–10% reduction in actively pretreated areas (p = 0.086). Immunohistochemical analysis in 2 patients revealed an induction of interferon-γ in primecrolimus-pretreated skin. Conclusion: APT can be used as a model for AE skin inflammation. It was shown for the first time that pimecrolimus pretreatment has a potential to suppress the development of lesions induced by aeroallergen exposure in patients with AE.

show abstract

Section: Discussionsupporting

confidence: 91%

Modulation of Atopy Patch Test and Skin Prick Test by Pretreatment with 1% Pimecrolimus Cream

Weissenbacher

Traidl‐Hoffmann

Eyerich

et al. 2006

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…This selective IDEC depletion phenomenon can also be induced by the topical calcineurin inhibitor pimecrolimus [59]. Topical hydrocortisone treatment increases the rate of early apoptotic DCs in situ, whereas topical tacrolimus does not [60]. Both agents decrease the expression of the costimulatory molecules CD80 and CD86 on epidermal DCs [60].…”

Section: Dendritic Cell Subsets In Ad Lesionsmentioning

confidence: 99%

Innate Immunity in Atopic Dermatitis

Wollenberg

Räwer

Schauber

2010

Clinic Rev Allerg Immunol

Self Cite

View full text Add to dashboard Cite

Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease. In AD patients, the combination of a genetic predisposition for skin barrier dysfunction and dysfunctional innate and adaptive immune responses leads to a higher frequency of bacterial and viral skin infections. The innate immune system quickly mobilizes an unspecific, standardized first-line defense against different pathogens. Defects in this system lead to barrier dysfunction which results in increased protein allergen penetration through the epidermis and predisposes to secondary skin infections. Two loss-of-function mutations in the epidermal filaggrin gene are associated with AD. Also, inducible endogenous antibiotics such as the antimicrobial peptides cathelicidin and the beta-defensins may show defective function in lesional AD skin. Eczema herpeticum is a disseminated viral infection almost exclusively diagnosed in AD patients, which is based on unmasking of the viral entry receptor nectin-1, lack of cathelicidin production by keratinocytes, and depletion of Type I IFN-producing plasmacytoid dendritic cells from AD skin. Future therapeutic approaches to AD may include enhancement of impaired innate in addition to downregulation of dysfunctional adaptive immunity.

show abstract

“…Indeed, it has recently been reported that apoptosis-resistant dendritic cells promote Th2 responses, including IgE production in an experimental mouse model [103]. Therapeutic approaches promoting dendritic cell apoptosis appear to be promising [104], further pointing to the possibility that the lifespan of dendritic cells is a critical element in the generation and/or maintenance of allergic diseases.…”

Section: Cell Death Of Dendritic Cellsmentioning

confidence: 99%

Cell death in allergic diseases

Simon

2009

Apoptosis

View full text Add to dashboard Cite

Apoptosis, the most common form of cell death, is a key mechanism in the build up and maintenance of both innate and adaptive immunity. Central to the apoptotic process is a family of intracellular cysteine proteases with aspartate-specificity, called caspases. Caspases are counter-regulated by multiple anti-apoptotic molecules, and the expression of the latter in leukocytes is largely dependent on survival factors. Therefore, the physiologic rates of apoptosis change under pathologic conditions. For instance, in inflammation, the expression of survival factors is usually elevated, resulting in increased cell survival and consequently in the accumulation of the involved immune cells. In many allergic diseases, eosinophil apoptosis is delayed contributing to both blood and tissue eosinophilia. Besides eosinophils, apoptosis of other leukocytes is also frequently prevented or delayed during allergic inflammatory processes. In contrast to inflammatory cells, accelerated cell death is often observed in epithelial cells, a mechanism, which amplifies or at least maintains allergic inflammation. In conclusion, deregulated cell death is a common phenomenon of allergic diseases that likely plays an important role in their pathogenesis. Whether the apoptosis is too little or too much depends on the cell type. In this review, we discuss the regulation of the lifespan of the participating leukocytes in allergic inflammatory responses.

show abstract

Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis

Cited by 56 publications

References 23 publications

Modulation of Atopy Patch Test and Skin Prick Test by Pretreatment with 1% Pimecrolimus Cream

Modulation of Atopy Patch Test and Skin Prick Test by Pretreatment with 1% Pimecrolimus Cream

Innate Immunity in Atopic Dermatitis

Cell death in allergic diseases

Contact Info

Product

Resources

About