Tumour necrosis factor blocking agents: a new therapeutic modality for inflammatory disorders

Abuzakouk, Mohamed; Feighery, Conleth; Jackson, Jennie

doi:10.1080/09674845.2002.11783656

Cited by 19 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30 Based on the pharmacological data available, huTNFR:Fc doses used in this study are well tolerated in humans. 5 …”

Section: Usage Of a Clinically Approved Anti-tnfa Drugmentioning

confidence: 99%

“…4 As a proinflammatory cytokine, tumor necrosis factor alpha (TNFa) is heavily implicated in the initiation and progression of autoimmune inflammatory disorders. 5,6 However, its role in Ad-induced toxicity has not been extensively studied. Although some studies found no elevation of TNFa following Ad injection, [7][8][9][10] other studies have found that TNFa release is in fact a consequence of higher-dose vector application in mice and nonhuman primates.…”

Section: Introductionmentioning

confidence: 99%

“…26,27 Here, we examine the role of TNFa in the development of acute and intermediate toxicity associated with systemic administration of Ad vectors. Based on the many studies validating the use of anti-TNFa therapy for disorders of inflammation 5 such as rheumatoid arthritis, psoriasis and Crohn's disease, [28][29][30] we also tested antiTNFa treatment as a palliative measure against Adinduced host inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of TNFα, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors

et al. 2006

View full text Add to dashboard Cite

Understanding the determinants of the host innate immune response to systemic administration of adenoviral (Ad) vectors is critical for clinical gene therapy. Acute toxicity occurs within minutes to hours after vector administration and is characterized by activation of innate immune responses. Our data indicate that in mice, indicators of vector toxicity include elevations of cytokine levels, liver transaminase levels and thrombocytopenia. To discern potential targets for blunting this host response, we evaluated genetic factors in the host response to systemically administered first-generation Ad vectors (FGV) and helper-dependent Ad vectors (HDV) containing b-galactosidase expression cassettes. A preliminary screen for modulation of vector-induced thrombocytopenia revealed no role for interferon-g, mast cells or perforin. However, vector-induced thrombocytopenia and interleukin 6 (IL-6) expression are less evident in tumor necrosis factor alpha (TNFa)-deficient mice. Moreover, we also demonstrated that TNFa blockade via antibody or huTNFR:Fc pretreatment attenuates both thrombocytopenia (440% increase in platelet count) and IL-6 expression (480% reduction) without affecting interleukin 12 , liver enzymes, hematological indices or vector transduction in a murine model. Our data indicate that the use of HDV, in combination with clinically approved TNFa immunomodulation, may represent an approach for improving the therapeutic index of Ad gene therapy for human clinical trials.

show abstract

“…30 Based on the pharmacological data available, huTNFR:Fc doses used in this study are well tolerated in humans. 5 …”

Section: Usage Of a Clinically Approved Anti-tnfa Drugmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of TNFα, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors

et al. 2006

View full text Add to dashboard Cite

show abstract

“…In patients with RA, AS or PsA, the introduction of anti-tumour necrosis factor (TNF)-a therapies such as etanercept, infliximab and adalimumab has had a significant impact in ameliorating the signs and symptoms of disease, improving patient function and inhibiting radiographic progression (10)(11)(12). Anti-TNF-a therapies now have well recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases (18), but such populations under-represent patients > or =65 years of age.…”

mentioning

confidence: 99%

The Safety of Anti-TNF Agents in the Elderly

Migliore

Bizzi

Laganà³

et al. 2009

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patient's twenties or thirties, they usually persist for the duration of the patient's life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.

show abstract

“…TNF is the prototypical proinflammatory cytokine (13). The overproduction of TNF has been associated with a number of autoimmune pathologies (14), and interfering with TNF production often ameliorates autoimmune manifestations (15). IL-12 production is associated with Th1 responses, and its role in host defense to intracellular pathogens has been well established (16).…”

mentioning

confidence: 99%

Innate Immune Responses to Rhodococcus equi

Darrah

Monaco

Jain

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

We examined innate immune responses to the intracellular bacterium Rhodococcus equi and show that infection of macrophages with intact bacteria induced the rapid translocation of NF-κB and the production of a variety of proinflammatory mediators, including TNF, IL-12, and NO. Macrophages from mice deficient in MyD88 failed to translocate NF-KB and produced virtually no cytokines in response to R. equi infection, implicating a TLR pathway. TLR4 was not involved in this response, because C3H/HeJ macrophages were fully capable of responding to R. equi infection, and because RAW-264 cells transfected with a dominant negative form of TLR4 responded normally to infection by R. equi. A central role for TLR2 was identified. A TLR2 reporter cell was activated by R. equi, and RAW-264 cells transfected with a dominant negative TLR2 exhibited markedly reduced cytokine responses to R. equi. Moreover, macrophages from TLR2−/− mice exhibited diminished cytokine responses to R. equi. The role of the surface-localized R. equi lipoprotein VapA (virulence-associated protein A), in TLR2 activation was examined. Purified rVapA activated a TLR2-specific reporter cell, and it induced the maturation of dendritic cells and the production of cytokines from macrophages. Importantly, TLR2−/−-deficient but not TLR4−/−-deficient mice were found to be compromised in their ability to clear a challenge with virulent R. equi. We conclude that the efficient activation of innate immunity by R. equi may account for the relative lack of virulence of this organism in immunocompetent adults.

show abstract

Tumour necrosis factor blocking agents: a new therapeutic modality for inflammatory disorders

Cited by 19 publications

References 0 publications

Modulation of TNFα, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors

Modulation of TNFα, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors

The Safety of Anti-TNF Agents in the Elderly

Innate Immune Responses to Rhodococcus equi

Contact Info

Product

Resources

About