Food allergy, dermatologic diseases, and anaphylaxisCytokines and chemokines orchestrate atopic skin inflammation
Section snippets
Overview of atopic skin immunology
Clinical observations in AD combined with the results of recent scientific studies suggest an amplification cycle of atopic skin inflammation (Fig 1). This cycle might start with pruritus, representing a prominent symptom of AD.2 Patients scratch and induce mechanical injury, resulting in proinflammatory cytokine and chemokine production. Subsequently, chemokines, in concert with an array of adhesion molecules, direct the recruitment of pathogenic leukocytes to the skin.3, 4, 5, 6 Within the
Production of primary proinflammatory cytokines
Little is known about the very early events initiating atopic skin inflammation. However, the production of primary proinflammatory cytokines after mechanical trauma and skin barrier disruption is a well-accepted scenario. Clinically, patients with AD show significantly lower itch thresholds and do not have skin lesions unless they scratch. Furthermore, experimental studies in mice support that the itch-scratch cycle is important for the development of dermatitis.17 Numerous studies showed that
Recruitment of pathogenic leukocyte subsets
Next to adhesion molecules, a new family of small cytokine-like proteins, the chemokines, has attracted significant interest with regard to understanding the mechanisms of leukocyte trafficking.25, 26, 27, 28 Chemokines are small (8-11 kd) chemotactic peptides that organize innate, as well as adaptive, immune responses.28 To date, 45 human chemokine ligands have been identified, and this superfamily is thought to be among the first functional protein families completely characterized at the
T-cell differentiation and activation
For nearly a decade, the concept of type 1 and type 2 (TH1 and TH2) T-cell responses has been applied to atopic diseases. Type 1 responses are initiated by IL-12 and characterized by T lymphocytes predominantly producing the effector cytokine IFN-γ. Conversely, type 2 T-cell differentiation is driven by IL-10 and prostaglandin E2 and characterized by the production of IL-4, IL-5, and IL-13. Overall, atopic diseases have been associated with a TH2 phenotype, showing dominance of IL-4, IL-5, and
Innate immune responses and the amplification of atopic skin inflammation
Evolutionary pressure developed and optimized an innate immune system to mount rapid responses against infectious agents through Toll-like receptors acting as pattern-recognition systems, antimicrobial peptides, or the production of proinflammatory cytokines.
Antimicrobial peptides known as cathelicidins (LL-37) and β-defensins represent another integral component of the innate immune system of human skin.13, 72, 73 The combination of cathelicidins and human β-defensin 2 shows synergistic
The complex network of mediators regulating pruritus in atopic individuals
Pruritus is an essential feature of AD, represents a bothersome symptom, and has a high effect on quality of life. In general, pruritus can be divided into 4 clinical categories: (1) pruritoceptive itch originating in the skin caused by inflammation, dryness, or skin damage; (2) neuropathic itch arising from diseases affecting the afferent neuronal pathways; (3) neurogenic itch developing in the central nervous system through mediation of μ-opioid receptors; and (4) psychogenic itch caused by
Conclusions and perspective
Recent insights into the complex network of cytokines and chemokines in AD might provide promising candidates for the diagnosis and molecular classification of subtypes of this disease. Furthermore, polymorphisms in cytokine or chemokine genes might represent susceptibility factors for the development of AD. Indeed, recent studies suggest a link; however, further studies with large and well-characterized patient and control collectives are necessary to confirm and validate these, as well as
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B. H. and T. R. are supported by grants of 5th frame work of the European Union and the German Research Foundation, the German Research Foundation (SFB 503). M. S. was supported by grants from the German Research Foundation (STE 1014, SFB 293), the Federal Ministry of Education and Research (IZKF), and CE.R.I.E.S. Paris.
Disclosure of potential conflict of interest: B. Homey has received grants/research support from the German Research Foundation and the German Cancer Foundation. D. Y. M. Leung has served on the speakers' bureau for Novartis and Astellas. The rest of the authors have declared that they have no conflict of interest.