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


: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.


Kaminitz A,Ash S,Askenasy N




Has Abstract


2017-06-01 00:00:00














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    authors: Conrad DJ

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    authors: Qamar N,Fuleihan RL

    更新日期:2014-04-01 00:00:00

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    authors: Sriaroon P,Ballow M

    更新日期:2016-04-01 00:00:00

  • A conspicuous role for B cells In Sjögren's syndrome.

    abstract::Although the relative contributions of T cells and B cells in Sjögren's syndrome (SS) are far from being settled, recent studies have suggested a crucial role for B cells in its pathophysiology. Early investigations have focused on the ability of B cells to produce autoantibodies, and new studies have enlarged the ran...

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    pub_type: 杂志文章,评审


    authors: Youinou P,Devauchelle V,Hutin P,Le Berre R,Saraux A,Pers JO

    更新日期:2007-06-01 00:00:00

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    authors: Hancox RJ

    更新日期:2006-10-01 00:00:00

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    journal_title:Clinical reviews in allergy & immunology

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    authors: Hernandez DV,Schmaling KB

    更新日期:2004-10-01 00:00:00

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    journal_title:Clinical reviews in allergy & immunology

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    authors: Albertson TE,Sutter ME,Chan AL

    更新日期:2015-02-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Murphy GF

    更新日期:2007-10-01 00:00:00

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    journal_title:Clinical reviews in allergy & immunology

    pub_type: 杂志文章,评审


    authors: Voter KZ,Ren CL

    更新日期:2008-12-01 00:00:00

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    abstract::Prognosis of several autoimmune diseases, especially rheumatoid arthritis (RA), ankylosing spondylitis, Crohn's disease (CD), and psoriasis, usually refractory to conventional treatment improved considerably with the introduction of tumor necrosis factor alpha (TNF-alpha) antagonistic agents, which is now available (i...

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    pub_type: 杂志文章,评审


    authors: Emi Aikawa N,de Carvalho JF,Artur Almeida Silva C,Bonfá E

    更新日期:2010-04-01 00:00:00

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    abstract::Reduced bone mineral density is frequently found especially in adult celiac disease (CD) and dietary guidelines favor vitamin D supplementation in adults and children with CD. Vitamin D serum levels were investigated in CD populations in order to challenge its routine supplementation. Israeli (61), Spanish (59), CD ch...

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    pub_type: 杂志文章


    authors: Lerner A,Shapira Y,Agmon-Levin N,Pacht A,Ben-Ami Shor D,López HM,Sanchez-Castanon M,Shoenfeld Y

    更新日期:2012-06-01 00:00:00

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    authors: Chiang DT,Clark J,Casale TB

    更新日期:2005-08-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Bassi N,Zampieri S,Ghirardello A,Tonon M,Zen M,Cozzi F,Doria A

    更新日期:2009-08-01 00:00:00

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    authors: Fijen LM,Bork K,Cohn DM

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    pub_type: 杂志文章,评审


    authors: Avdalovic M

    更新日期:2015-02-01 00:00:00

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    journal_title:Clinical reviews in allergy & immunology

    pub_type: 杂志文章,评审


    authors: Borish L,Rosenwasser L,Steinke JW

    更新日期:2006-06-01 00:00:00

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    abstract::The critical asthma syndrome (CAS) encompasses the most severe, persistent, refractory asthma patients for the clinician to manage. Personalized pharmacotherapy is necessary to prevent the next acute severe asthma exacerbation, not just the control of symptoms. The 2007 National Asthma Education and Prevention Program...

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    pub_type: 杂志文章,评审


    authors: Albertson TE,Schivo M,Gidwani N,Kenyon NJ,Sutter ME,Chan AL,Louie S

    更新日期:2015-02-01 00:00:00

  • Autoinflammatory Pathogenesis and Targeted Therapy for Adult-Onset Still's Disease.

    abstract::Adult-onset Still's disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology. AOSD is generally characterized by high spiking fever, arthralgia or arthritis, skin rash, leukocytosis, and hyperferritinemia. Traditionally, AOSD has been treated with non-steroidal anti-inflammatory drugs, cortic...

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    pub_type: 杂志文章,评审


    authors: Li S,Zheng S,Tang S,Pan Y,Zhang S,Fang H,Qiao J

    更新日期:2020-02-01 00:00:00

  • Vasculitides and the Complement System: a Comprehensive Review.

    abstract::Systemic vasculitides are a group of rare diseases characterized by inflammation of the arterial or venous vessel wall, causing stenosis or thrombosis. Clinical symptoms may be limited to skin or to other organs or may include multiple manifestations as systemic conditions. The pathogenesis is related to the presence ...

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    authors: Chimenti MS,Ballanti E,Triggianese P,Perricone R

    更新日期:2015-12-01 00:00:00

  • Increased prevalence of anti-third generation cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis and CREST syndrome.

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    authors: Wu R,Shovman O,Zhang Y,Gilburd B,Zandman-Goddard G,Shoenfeld Y

    更新日期:2007-02-01 00:00:00

  • The Roles of Orphan G Protein-Coupled Receptors in Autoimmune Diseases.

    abstract::G protein-coupled receptors (GPCRs) constitute the largest family of plasma membrane receptors in nature and mediate the effects of a variety of extracellular signals, such as hormone, neurotransmitter, odor, and light signals. Due to their involvement in a broad range of physiological and pathological processes and t...

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    pub_type: 杂志文章,评审


    authors: Zhao M,Wang Z,Yang M,Ding Y,Zhao M,Wu H,Zhang Y,Lu Q

    更新日期:2021-01-07 00:00:00

  • Fractional Exhaled Nitric Oxide for the Diagnosis of Childhood Asthma: a Systematic Review and Meta-analysis.

    abstract::The gold standard for diagnosing asthma in children is based on clinical history of respiratory symptoms, physical examination, and respiratory function testing. Recent advances indicate that a non-invasive measure of airway inflammation, fractional exhaled nitric oxide (FeNO), provides objective data for use in asthm...

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    pub_type: 杂志文章,meta分析


    authors: Tang S,Xie Y,Yuan C,Sun X,Cui Y

    更新日期:2019-04-01 00:00:00

  • B-cell depletion in Wegener's granulomatosis.

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    authors: Hinze CH,Colbert RA

    更新日期:2008-06-01 00:00:00

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    authors: Goropevšek A,Holcar M,Avčin T

    更新日期:2017-04-01 00:00:00

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    authors: Maharajan MK,Ranjan A,Chu JF,Foo WL,Chai ZX,Lau EY,Ye HM,Theam XJ,Lok YL

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    authors: Niimi A,Matsumoto H,Takemura M,Ueda T,Nakano Y,Mishima M

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    authors: Verma AK,Kumar S,Das M,Dwivedi PD

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    authors: Pollmann R,Schmidt T,Eming R,Hertl M

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    authors: Tilles SA,Bardana EJ Jr

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    authors: Beuers U,Kullak-Ublick GA,Pusl T,Rauws ER,Rust C

    更新日期:2009-02-01 00:00:00