Potential of Tumor Necrosis Factor Inhibitors in Psoriasis and Psoriatic Arthritis

Krueger, Gerald G.; Callis, Kristina P.

doi:10.1001/archderm.140.2.218

Cited by 84 publications

(74 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TNF-␣, a type 1 and inflammatory cytokine, is increased in psoriatic skin lesions (71). TNF-␣ is produced by various types of cells, including Th1 cells, mast cells, macrophages, DCs, and keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis

Toichi

Torres

McCormick

et al. 2006

The Journal of Immunology

188

126

View full text Add to dashboard Cite

Psoriasis is characterized by activation of T cells with a type 1 cytokine profile. IL-12 and IL-23 produced by APCs are essential for inducing Th1 effector cells. Promising clinical results of administration of an Ab specific for the p40 subunit of IL-12 and IL-23 (anti-IL-12p40) have been reported recently. This study evaluated histological changes and mRNA expression of relevant cytokines and chemokines in psoriatic skin lesions following a single administration of anti-IL-12p40, using immunohistochemistry and real-time RT-PCR. Expression levels of type 1 cytokine (IFN-γ) and chemokines (IL-8, IFN-γ-inducible protein-10, and MCP-1) were significantly reduced at 2 wk posttreatment. The rapid decrease of these expression levels preceded clinical response and histologic changes. Interestingly, the level of an anti-inflammatory cytokine, IL-10, was also significantly reduced. Significant reductions in TNF-α levels and infiltrating T cells were observed in high responders (improvement in clinical score, ≥75% at 16 wk), but not in low responders. Of importance, the levels of APC cytokines, IL-12p40 and IL-23p19, were significantly decreased in both responder populations, with larger decreases in high responders. In addition, baseline levels of TNF-α significantly correlated with the clinical improvement at 16 wk, suggesting that these levels may predict therapeutic responsiveness to anti-IL-12p40. Thus, in a human Th1-mediated disease, blockade of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23 themselves, with a pattern indicative of coordinated deactivation of APCs and Th1 cells.

show abstract

Section: Discussionmentioning

confidence: 99%

An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis

Toichi

Torres

McCormick

et al. 2006

The Journal of Immunology

188

126

View full text Add to dashboard Cite

show abstract

“…Tumor necrosis factor ␣ is a proinflammatory cytokine released by macrophages, mastocytes, keratinocytes, and fibroblasts in response to environmental injury or microbial invasion. 27 It induces other chemokines, which attract neutrophils, macrophages, and memory T cells to the site of injury. 27 Tumor necrosis factor ␣ is also one of the major fibrotic cytokines along with interleukin 1, platelet-derived growth factor, fibroblast growth factor, and transforming growth factor ␤, and it has been shown to stimulate the growth of fibroblasts.…”

Section: Commentmentioning

confidence: 99%

Successful Treatment of Mucous Membrane Pemphigoid With Etanercept in 3 Patients

Canizares

Smith²,

Conners³

et al. 2006

Arch Dermatol

View full text Add to dashboard Cite

“…Multiple clinical trials have demonstrated the success of this competitive inhibitor of TNF-a binding to its cognate receptor in ameliorating diseases, in which chronic inflammation plays a pathophysiologic role, including Crohn's disease, juvenile arthritis, adult rheumatoid arthritis and psoriatic diseases. [6][7][8] Treatment with enbrel results in reduction in multiple proinflammatory cytokines and adhesion molecules, decreases cell trafficking and angiogenesis, and halts joint destruction. 6 The E1B-19K and E3B viral genes encoded by the wild-type adenovirus are functionally redundant with respect to their capacity to antagonize TNF-a induction, thereby contributing to enhanced viral replication and spread.…”

Section: Introductionmentioning

confidence: 99%

A phase I trial of intravenous infusion of ONYX-015 and enbrel in solid tumor patients

et al. 2007

View full text Add to dashboard Cite

ONYX-015 is an attenuated chimeric human group C adenovirus, which preferentially replicates in and lyses tumor cells that are p53 negative. The purpose of this phase I, dose-escalation study was to determine the safety and feasibility of intravenous infusion with ONYX-015 in combination with enbrel in patients with advanced carcinoma. Enbrel is a recombinant dimer of human tumornecrosis factor (TNF)-a receptor, previously shown to reduce the level of functional TNF. Nine patients, three in each cohort received multiple cycles of ONYX-015 infusion (1 Â 10 10 , 1 Â 10 11 and 1 Â 10 12 vp weekly for 4 weeks/cycle) in addition to subcutaneous enbrel (only during cycle 1) injections per FDA-indicated dosing. Of the nine patients, four had stable disease. No significant adverse events were attributed to the experimental regimen, confirming that enbrel can be safely administered along with oncolytic virotherapy. Two of the three patients in cohort 3 had detectable viral DNA at days 3 and 8 post-ONYX-015 infusion. Their detectable circulating viral DNA was markedly higher during cycle 1 (with enbrel coadministration) as compared with cycle 2 (without enbrel) at the same time points. Area under the curve determinations indicate a marked higher level of TNF-a induction and accelerated clearance at cycle 2 in the absence of enbrel. Further assessment is recommended.

show abstract

Potential of Tumor Necrosis Factor Inhibitors in Psoriasis and Psoriatic Arthritis

Cited by 84 publications

References 93 publications

An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis

An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis

Successful Treatment of Mucous Membrane Pemphigoid With Etanercept in 3 Patients

A phase I trial of intravenous infusion of ONYX-015 and enbrel in solid tumor patients

Contact Info

Product

Resources

About