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The role of eosinophils in the pathogenesis of atopic dermatitis ‐ eosinophil granule proteins as markers of disease activity

Alexander Kapp

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Abstract

Currently, there is a large body of evidence that atopic dermatitis (AD) has an immunologic basis. Atopy-specific helper T cells (Th2-like T cells) may play a pathogenetic role by producing and releasing cytokines relevant for the allergic inflammation, such as IL-4, IL-5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically relevant late-phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL-5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD.

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What this paper is about

Currently, there is a large body of evidence that atopic dermatitis (AD) has an immunologic basis. Atopy-specific helper T cells (Th2-like T cells) may play a pathogenetic role by producing and releasing cytokines relevant for the allergic inflammation, such as IL-4, IL-5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically relevant late-phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL-5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD.

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Available abstract

Currently, there is a large body of evidence that atopic dermatitis (AD) has an immunologic basis. Atopy-specific helper T cells (Th2-like T cells) may play a pathogenetic role by producing and releasing cytokines relevant for the allergic inflammation, such as IL-4, IL-5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically relevant late-phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL-5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD.

Key concepts: Immunology, Eosinophil Granule Proteins, Eosinophil cationic protein, Eosinophil, Atopy, Atopic dermatitis, Major basic protein, Medicine

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