Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon

Solórzano, Carmen C.; Kaibara, Atsushi; Heß, Peter; Edwards, Paul D.; Ksontini, Riadh; Abouhamze, Amer; McDaniel, Sherry; Frazier, Janet; Trujillo, D.; Kieft, G.; Seely, James E.; Kohno, Tadahiko; Cosenza, Mary Ellen; Clare‐Salzler, Michael; MacKay, Sally L. D.; Martin, Steven W.; Moldawer, Lyle L.; Edwards, Carl K.

doi:10.1152/jappl.1998.84.4.1119

Cited by 35 publications

(38 citation statements)

References 29 publications

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“…Fifteen days after adjuvant injection, 20 control and 24 arthritic rats were divided into two groups, one injected daily with 1 mg/kg s.c. PEG-sTNFRI (Amgen Inc, Thousand Oaks, CA, USA) and the other with 250 ml saline, until day 22 after adjuvant injection. At this dose, this TNF-binding complex is able to block the systemic TNF-a response (evaluated by its cytotoxicity activity) as well as plasma TNF-a bioactivity in baboons challenged with a lethal Escherichia coli bacteraemia (Solorzano et al 1998). Assessment of arthritis was performed by measuring the arthritis index of each animal, which was scored by grading each paw from 0 to 4.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

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Chronic inflammation is associated with a decrease in body weight and cachexia, which is characterized by anorexia and skeletal muscle wasting. The expression of atrogens muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) are increased in muscle atrophy and it is known that tumour necrosis factor (TNF) regulates skeletal muscle loss through TNF receptor p55 (TNFRI). The aim of this study was to examine the effect of polyethylene glycol linked to soluble TNFRI (PEG-sTNFRI) on gene expression of the atrogens MuRF-1 and MAFbx in skeletal muscle of arthritic rats. Rats were injected with Freund's adjuvant and, 15 days later, arthritic and control rats were injected daily with PEG-sTNFRI (1 mg/kg, s.c.) or saline for 8 days. Arthritis decreased body weight gain, the weight of skeletal muscle and adipose mass. PEG-sTNFRI administration increased body weight gain and adipose mass of arthritic rats; however, it did not modify the skeletal muscle weight. The gene expression of TNF-a, MuRF1 and MAFbx, IGF-I and IGFBP-5 were increased in the skeletal muscle of arthritic rats, and the administration of PEG-sTNFRI did not modify these parameters. These data suggest that the anti-TNF agent PEG-sTNFRI did not prevent the increase in E3 ubiquitinligating enzymes, MuRF1 and MAFbx, gene expression in the skeletal muscle of arthritic rats.

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Section: Animals and Experimental Designmentioning

confidence: 99%

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

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“…The TNF-bp used contained the extracellular domain of the human TNF receptor I (p55) (Amgen, Thousand Oaks, CA, USA). 17 …”

Section: Tnf-binding Protein (Bp)mentioning

confidence: 99%

Influence of recombinant adenovirus on liver injury in endotoxicosis and its modulation by IL-10 expression

Oberholzer

Tschoeke

et al. 2004

Journal of Endotoxin Research

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Adenovirus-based gene therapy offers a unique opportunity to target gene expression to the liver by systemic delivery. However, systemic administration of a first generation adenoviral construct elicits an inflammatory response leading to TNF-α-dependent liver injury. The aim of this study was to evaluate whether the systemic administration of recombinant adenovirus exacerbates a subsequent TNF-α-dependent liver injury induced by D-galactosamine and lipopolysaccharide. Surprisingly, low-dose adenovirus administration (10 5 particles) protects, while high-dose adenovirus (10 10 particles) is associated with an exaggerated hepatic inflammatory response from a subsequent D-galactosamine and lipopolysaccharide challenge. This exacerbation is TNF-α dependent, since treatment with a TNF inhibitor fully protects against the liver injury. Moreover, intravenous administration of an adenoviral construct expressing the anti-inflammatory protein interleukin-10 reduces TNF-α appearance and attenuates the increased hepatocyte injury. Taken together, this report demonstrates potential additive effects of TNF-α responses induced by adenovirus and other inflammatory signals, and suggests that the response can be mitigated by relative adenovirus particle dose or by inhibitors, such as TNF-binding protein or interleukin 10.

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“…To determine whether a humoral response develops against the expressed ␤-galactosidase or human IL-10, a direct ELISA for Abs (IgG) was performed (34). Briefly, recombinant ␤-galactosidase (Sigma, St. Louis, MO) or human IL-10 (Schering-Plough Research Laboratories, Kenilworth, NJ) was coated onto 96-well Corning flat-bottom, polystyrene ELISA plates (0.5 g/ml).…”

Section: Adenovirus and ␤-Galactosidase Ab Measurementsmentioning

confidence: 99%

TNF-α Receptor Signaling and IL-10 Gene Therapy Regulate the Innate and Humoral Immune Responses to Recombinant Adenovirus in the Lung

Minter¹,

Rectenwald²,

Fukuzuka³

et al. 2000

The Journal of Immunology

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Recombinant adenovirus-mediated gene therapy has demonstrated great promise for the delivery of genes to the pulmonary epithelium. However, dose-dependent inflammation and local immune responses abbreviate transgene expression. The purpose of these studies was to determine the role of TNF-α and individual TNF receptor signaling to adenovirus clearance and immune responses, and whether coexpression of human IL-10 could reduce inflammation and extend the duration of transgene expression in the lung. β-Galactosidase expression in mice receiving intratracheal instillation of Adv/β-gal (adenovirus construct expressing β-galactosidase) was transient (less than 14 days), but a significant early increase of β-galactosidase expression was seen in mice lacking either or both TNF-α receptors. Absence of TNF-α or the p55 receptor significantly attenuated the Ab response to both adenovirus and β-galactosidase. Human IL-10 expression in the lung suppressed local TNF-α production following AdV/hIL-10 (adenovirus construct expressing human IL-10) delivery, but did not lead to increased or prolonged transgene expression when coexpressed with β-galactosidase. Expression of human IL-10 following AdV/hIL-10 instillation extended at least 14 days, was nonimmunogenic, and suppressed the development of neutralizing Abs against adenoviral proteins as well as against human IL-10. We conclude that TNF-α signaling through both the p55 and p75 receptor plays important roles in the clearance of adenoviral vectors and the magnitude of the humoral immune response. Additionally, although coexpression of human IL-10 with β-galactosidase had only modest effects on transgene expression, we demonstrate that AdV/hIL-10 is well tolerated, has extended expression compared with β-galactosidase, and is nonimmunogenic in the lung.

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Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon

Cited by 35 publications

References 29 publications

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Influence of recombinant adenovirus on liver injury in endotoxicosis and its modulation by IL-10 expression

TNF-α Receptor Signaling and IL-10 Gene Therapy Regulate the Innate and Humoral Immune Responses to Recombinant Adenovirus in the Lung

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