Infliximab Treatment of Rheumatoid Arthritis and Crohn's Disease

Nahar, Ibrahim; Shojania, Kam; Marra, Carlo A.; Alamgir, Abul H.; Anis, Aslam H.

doi:10.1345/aph.1c039

Cited by 72 publications

(30 citation statements)

References 40 publications

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“…Cytokine inhibition with a soluble receptor or antibody against the ligand or its receptor is an essential clinical approach for therapeutic purposes (19)(20)(21). Thus, it will be of great interest to determine the most active domain of IL-32 in order to elucidate a potential target for IL-32 inhibition, which would be beneficial for the treatment of chronic respiratory diseases.…”

Section: Discussionmentioning

confidence: 99%

Proteinase 3-processed form of the recombinant IL-32 separate domain

Kim

Lee²,

Her³

et al. 2008

BMB Reports

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Section: Discussionmentioning

confidence: 99%

Proteinase 3-processed form of the recombinant IL-32 separate domain

Kim

Lee²,

Her³

et al. 2008

BMB Reports

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“…Neutralizing Abs to IL-1/TNF were found to be beneficial in diseases associated with excessive IL-1/TNF production (51,52). Clinical trials with mAb against TNF-␣ that focused on rheumatoid arthritis and Crohn's disease have demonstrated promising results (53). Second, administration of IL-1 receptor antagonist, the natural antagonist to IL-1, was shown to improve recovery after traumatic injury (25,54).…”

Section: Discussionmentioning

confidence: 99%

Short- and Long-Term Effects of IL-1 and TNF Antagonists on Periodontal Wound Healing

Zhang

Kohli

Zhou

et al. 2004

The Journal of Immunology

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The present study tested the effects of local injection of IL-1 and TNF soluble receptors on a periodontal wound-healing model in nonhuman primates. In this model, periodontal lesions were developed for 16 wk, followed by open flap surgery. Starting at the time of surgery, groups of animals received localized injections of both soluble cytokine receptors or else PBS three times per week for 3, 14, or 35 days. Periodontal wound healing was analyzed for each group at the end of the treatment regimen. Fourteen days after surgery, a significant decrease was observed between the animals treated with soluble receptors and the untreated group with respect to recruitment of inflammatory cells in deep gingival connective tissue. Concurrent apoptosis of inflammatory cells in those tissues increased significantly in treated animals compared with untreated animals. All other outcome parameters of periodontal wound healing were likewise significantly improved in treated animals compared with untreated animals. In marked contrast, however, 35 days after surgery, there was a significant increase in the number of inflammatory cells that had infiltrated into deep gingival connective tissue in treated compared with untreated animals. Outcome parameters of periodontal wound healing worsened in treated animals when compared with untreated. These results indicate that proinflammatory cytokines may play different functional roles in early vs late phases of periodontal wound healing. Short-term blockade of IL-1 and TNF may facilitate periodontal wound healing, whereas prolonged blockade may have adverse effects.

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“…However, the wide spectrum of processes affected by TNF␣ precludes our understanding and predicting fully the effects and side effects of the TNF␣-targeted therapies. Overinhibiting the TNF␣ signals has a potential risk of delaying wound healing, secondary infections, and cancer; indeed, increased risks of tuberculosis and carcinogenesis have been reported as side effects after anti-TNF␣ therapy (3,4). We believe that the dissection and comprehensive characterization of the pathways and genes regulated by TNF␣ will identify even more specific and finely tuned targets, which affect only a particular, defined subset of the TNF␣-regulated genes.…”

Section: Tnf␣mentioning

confidence: 99%

Pathway-specific Profiling Identifies the NF-κB-dependent Tumor Necrosis Factor α-regulated Genes in Epidermal Keratinocytes

Banno

Gazel²,

Blumenberg

2005

Journal of Biological Chemistry

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Identification of tumor necrosis factor ␣ (TNF␣) as the key agent in inflammatory disorders led to new therapies specifically targeting TNF␣ and avoiding many side effects of earlier anti-inflammatory drugs. However, because of the wide spectrum of systems affected by TNF␣, drugs targeting TNF␣ have a potential risk of delaying wound healing, secondary infections, and cancer. Indeed, increased risks of tuberculosis and carcinogenesis have been reported as side effects after anti-TNF␣ therapy. TNF␣ regulates many processes (e.g. immune response, cell cycle, and apoptosis) through several signal transduction pathways that convey the TNF␣ signals to the nucleus. Hypothesizing that specific TNF␣-dependent pathways control specific processes and that inhibition of a specific pathway may yield even more precisely targeted therapies, we used oligonucleotide microarrays and parthenolide, an NF-B-specific inhibitor, to identify the NF-B-dependent set of the TNF␣-regulated genes in human epidermal keratinocytes. Expression of ϳ40% of all TNF␣-regulated genes depends on NF-B; 17% are regulated early (1-4 h post-treatment), and 23% are regulated late (24 -48 h). Cytokines and apoptosisrelated and cornification proteins belong to the "early" NF-B-dependent group, and antigen presentation proteins belong to the "late" group, whereas most cell cycle, RNA-processing, and metabolic enzymes are not NF-Bdependent. Therefore, inflammation, immunomodulation, apoptosis, and differentiation are on the NF-B pathway, and cell cycle, metabolism, and RNA processing are not. Most early genes contain consensus NF-B binding sites in their promoter DNA and are, presumably, directly regulated by NF-B, except, curiously, the cornification markers. Using siRNA silencing, we identified cFLIP/CFLAR as an essential NF-B-dependent antiapoptotic gene. The results confirm our hypothesis, suggesting that inhibiting a specific TNF␣-dependent signaling pathway may inhibit a specific TNF␣-regulated process, leaving others unaffected. This could lead to more specific anti-inflammatory agents that are both more effective and safer.

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Infliximab Treatment of Rheumatoid Arthritis and Crohn's Disease

Cited by 72 publications

References 40 publications

Proteinase 3-processed form of the recombinant IL-32 separate domain

Proteinase 3-processed form of the recombinant IL-32 separate domain

Short- and Long-Term Effects of IL-1 and TNF Antagonists on Periodontal Wound Healing

Pathway-specific Profiling Identifies the NF-κB-dependent Tumor Necrosis Factor α-regulated Genes in Epidermal Keratinocytes

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