2000
DOI: 10.1007/pl00000629
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Anti-interleukin-1 and anti-tumor necrosis factor-α synergistically inhibit adjuvant arthritis in Lewis rats

Abstract: Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) play dominant roles in mediating the progression of many inflammatory joint diseases, including rheumatoid arthritis in humans, collagen-induced arthritis in mice and rats, and adjuvant arthritis in rats. Blockade of either cytokine partially controls these diseases. The present study investigated the value of combination anti-cytokine therapy in arthritis: the efficacy of IL-1 receptor antagonist (IL-1ra) and 30 kDa polyethylene glycol (PEG)-con… Show more

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Cited by 108 publications
(116 citation statements)
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“…Minipumps were implanted in the dorsal subcutis, and wounds were sealed using steel clips. Doses of IL-1Ra and PEG sTNFRI were selected based on previous studies (12) demonstrating that these doses, routes, and schedule cover the region of the dose-response curve ranging from (almost) inactive to fully active against the severe polyarthritis characteristic of the AIA model in Lewis rats. In particular, we have shown that IL-1Ra (5 mg/kg/hour) and PEG sTNFRI (4 mg/kg/day) yield comparable antiinflammatory and bone-sparing effects when given for 7 days.…”
Section: Methodsmentioning
confidence: 99%
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“…Minipumps were implanted in the dorsal subcutis, and wounds were sealed using steel clips. Doses of IL-1Ra and PEG sTNFRI were selected based on previous studies (12) demonstrating that these doses, routes, and schedule cover the region of the dose-response curve ranging from (almost) inactive to fully active against the severe polyarthritis characteristic of the AIA model in Lewis rats. In particular, we have shown that IL-1Ra (5 mg/kg/hour) and PEG sTNFRI (4 mg/kg/day) yield comparable antiinflammatory and bone-sparing effects when given for 7 days.…”
Section: Methodsmentioning
confidence: 99%
“…Adjuvant arthritis was induced in adult male Lewis rats weighing 180-200 gm (n ϭ 6 per group) on day 0 as described (12), by a single intradermal injection, at the tail base, of heat-killed Mycobacterium tuberculosis H37Ra (0.5 mg; Difco, Detroit, MI) suspended in 0.05 ml paraffin oil (Crescent Chemical, Islandia, NY). A refined volume displacement method (12) was used beginning on day 8 to measure hind paw volume to determine the clinical onset of arthritis.…”
Section: Methodsmentioning
confidence: 99%
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“…As inflammation progresses in the joint, increased levels of IL-4, IL-6, monocyte chemotactic protein 1 (MCP-1)/CCL2, and TGF␤ can be detected (34). TNF␣, IL-1␤, IL-21, and IL-17 are all involved in the pathology of this disease, because their blockade ameliorates disease (35)(36)(37). AIA is not joint-specific but is associated with granuloma formation in various organs and tissues, such as the spleen, liver, bone marrow, skin, and eyes (38).…”
Section: Evaluation Of Therapeutic Targets In Animal Models Of Arthritismentioning
confidence: 99%