Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases

Hallegua, David S.; Weisman, M H

doi:10.1136/ard.61.11.960

Cited by 81 publications

(58 citation statements)

References 54 publications

(35 reference statements)

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“…In these arthritis mouse models, IL-1β exerted a key role in mediating inflammation. Similarly, in humans, TNF-α therapy alone or with concomitant methotrexate is effective in no more than 40% of patients with RA at 30 weeks of treatment (American College of Rheumatology 50% improvement criteria) (44,45), and IL-1β inhibitors have a moderate effect (46). These results suggest the importance of the balance between proand anti-inflammatory cytokines, which is not dependent on a single cytokine (15).…”

Section: Discussionmentioning

confidence: 64%

CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

Sancho¹,

Gómez²,

Viedma³

et al. 2003

J. Clin. Invest.

152

111

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CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69 -/-mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-β1 and TGF-β2, which act as protective agents in CIA, were reduced in CD69 -/-mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1β and RANTES. Local injection of blocking anti-TGF-β antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69 +/+ but not in CD69 -/-mice. Moreover, in vitro engagement of CD69 induced total and active TGF-β1 production in Concanavalin A-activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-β, a cytokine that in turn downregulates the production of various proinflammatory mediators.

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Section: Discussionmentioning

confidence: 64%

CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

Sancho¹,

Gómez²,

Viedma³

et al. 2003

J. Clin. Invest.

152

111

View full text Add to dashboard Cite

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“…Thus, IL-1 is not a dispensable cytokine downstream of TLR4, and its signaling pathway is an essential component of the immune response to B. pertussis infection. Blocking IL-1 secretion or IL-1R-mediated signaling has been a proposed treatment of chronic inflammatory diseases, such as rheumatoid arthritis and Crohn's disease (6,25). Some respiratory infections have been identified in patients using drugs blocking IL-1R signaling (22).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor Signaling Is Required To Overcome the Effects of Pertussis Toxin and for Efficient Infection- or Vaccination-Induced Immunity against Bordetella pertussis

et al. 2011

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Interleukin-1 receptor-deficient (IL-1R؊/؊ ) mice are healthy despite being colonized by commensal microbes but are defective in defenses against specific pathogens, suggesting that IL-1R-mediated effects contribute to immune responses against specific pathogenic mechanisms. To better define the role of IL-1R in immunity to respiratory infections, we challenged IL-1R؊/؊ mice with Bordetella pertussis and Bordetella parapertussis, the causative agents of whooping cough. Following inoculation with B. pertussis, but not B. parapertussis, IL-1R ؊/؊ mice showed elevated bacterial numbers and more extensive inflammatory pathology than wild-type mice. Acellular B. pertussis vaccines were not efficiently protective against B. pertussis in IL-1R ؊/؊ mice. B. pertussisstimulated dendritic cells from IL-1R؊/؊ mice produced higher levels of tumor necrosis factor alpha (TNF-␣) and IL-6 than wild-type cells. Moreover, elevated levels of gamma interferon (IFN-␥) and TNF-␣ but lower levels of IL-10 were detected during B. pertussis infection in IL-1R

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“…Activated IKK phosphorylates I-B, which then is recognized and destroyed by the proteasome pathway. Consequently, NF-B is released and enters into the nucleus to turn on several genes that regulate cell growth and apoptosis and inflammation, particularly those encoding IL-1 and IL-6 [33,34]. Therefore, it is conceivable that IL-1 and IL-6 are both overexpressed in CD because of a common aberrant upstream regulator or, alternatively, that upregulation of IL-1 stimulates IL-6.…”

Section: Role Of Il-1 and Nf-bmentioning

confidence: 99%

Castleman's Disease: From Basic Mechanisms to Molecular Therapeutics

2011

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Castleman's disease is a rare lymphoproliferative disorder in which there has been recent progress in elucidating underlying mechanisms with potential therapeutic implications. Unicentric Castleman's disease is an indolent condition that is often treated with local approaches. In contrast, patients with multicentric Castleman's disease (MCD) have a less favorable prognosis and require systemic treatment. Cytotoxic chemotherapy, with its attendant risk for toxicity, has been widely used to treat MCD, with variable efficacy. The discovery of putative etiologic factors and targets in MCD, particularly human herpes virus 8, CD20, and interleukin (IL)-6, has been translated into the use of rituximab and anti-IL-6-based therapy, as well as antiviral agents. In this article, we review the current state of the art of our understanding of Castleman's disease and its treatment and we provide insight into future treatment strategies based on disease biology. The Oncologist 2011;16:497-511

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Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases

Cited by 81 publications

References 54 publications

CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

Interleukin-1 Receptor Signaling Is Required To Overcome the Effects of Pertussis Toxin and for Efficient Infection- or Vaccination-Induced Immunity against Bordetella pertussis

Castleman's Disease: From Basic Mechanisms to Molecular Therapeutics

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