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Clinical Reviews in Allergy & Immunology
Erschienen in: Clinical Reviews in Allergy & Immunology 3/2017

27.09.2016

Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes

verfasst von: Ayelet Kaminitz, Shifra Ash, Nadir Askenasy

Erschienen in: Clinical Reviews in Allergy & Immunology | Ausgabe 3/2017

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Abstract

As physiological pathways of intercellular communication produced by all cells, cytokines are involved in the pathogenesis of inflammatory insulitis as well as pivotal mediators of immune homeostasis. Proinflammatory cytokines including interleukins, interferons, transforming growth factor-β, tumor necrosis factor-α, and nitric oxide promote destructive insulitis in type 1 diabetes through amplification of the autoimmune reaction, direct toxicity to β-cells, and sensitization of islets to apoptosis. The concept that neutralization of cytokines may be of therapeutic benefit has been tested in few clinical studies, which fell short of inducing sustained remission or achieving disease arrest. Therapeutic failure is explained by the redundant activities of individual cytokines and their combinations, which are rather dispensable in the process of destructive insulitis because other cytolytic pathways efficiently compensate their deficiency. Proinflammatory cytokines are less redundant in regulation of the inflammatory reaction, displaying protective effects through restriction of effector cell activity, reinforcement of suppressor cell function, and participation in islet recovery from injury. Our analysis suggests that the role of cytokines in immune homeostasis overrides their contribution to β-cell death and may be used as potent immunomodulatory agents for therapeutic purposes rather than neutralized.
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Metadaten
Titel
Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes
verfasst von
Ayelet Kaminitz
Shifra Ash
Nadir Askenasy
Publikationsdatum
27.09.2016
Verlag
Springer US
Erschienen in
Clinical Reviews in Allergy & Immunology / Ausgabe 3/2017
Print ISSN: 1080-0549
Elektronische ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-016-8587-y

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