Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist

Eisenberg, Stephen P.; Evans, Ron J.; Arend, William P.; Verderber, Evie L.; Brewer, Michael K.; Hannum, Charles; Thompson, Robert C.

doi:10.1038/343341a0

Cited by 1,040 publications

(389 citation statements)

References 43 publications

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“…is IL-lra is a 23-to 25-KD glycosylated protein, originally purified from supernatants of human monocytes cultured on immune complexcoated surfaces, 14 or from the urine of patients with monocytic leukaemia, which has been recently cloned. 16 The IL-lra specifically blocks IL-11~ and IL-111 at its receptor level. 17 The excessive production of IL-6 and IL-8 may be inhibited by suppression of this excessive local production of IL-1.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 and Interleukin-1 receptor antagonists increase during cardiac surgery

1997

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Section: Discussionmentioning

confidence: 99%

Interleukin-10 and Interleukin-1 receptor antagonists increase during cardiac surgery

1997

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“…[2][3][4][5] The IL-1 receptor antagonist (IL-1Ra) is a natural protein that competitively inhibits the binding of IL-1b and IL-1a to IL-1 receptor types I and II in humans and various animals, and improves the inflammatory symptoms of arthritis in experimental animal models. 1,[6][7][8][9][10] Several independent clinical trials have been completed in which the recombinant IL-1Ra protein has been administered for a long-term period to patients with RA. 11,12 The results indicate that treatment with IL-1Ra lowers the levels of proteins involved in the acute phase of RA and the counts of swollen joints and, furthermore, may inhibit radiographic progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Jeong

et al. 2003

Gene Ther

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The interleukin-1 receptor antagonist (IL-1Ra) is an endogenous protein that can prevent the binding of IL-1 to its cellsurface receptors. Among a number of techniques for gene transfer in vivo, the direct injection of naked DNA into muscle is simple, inexpensive and safe. In this study, we evaluated the potential of intramuscular gene therapy with plasmid DNA containing the cDNA for IL-1Ra in the prevention of murine collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type II collagen. At 4 weeks after the initial immunization, expression plasmid for IL-1Ra was injected into four selected sites in the thigh and calf muscles of DBA/1 mice. Control mice received the same plasmid, but lacking the IL-1Ra coding sequence. Macroscopic analysis of paws for redness, swelling and deformities showed that the onset of moderate to severe CIA in the paws of mice injected with IL-1Ra DNA was significantly prevented (Po0.05). In addition, both the synovitis and the cartilage erosion in knee joints were dramatically reduced in mice treated with IL-1Ra DNA (Po0.05). The expression of IL-1b was significantly decreased in the ankle joints of mice treated with IL-1Ra (Po0.01). Interestingly, the levels of IL-1Ra in sera and joints after intramuscular injection of IL-1Ra DNA were significantly lower than when protein had been used in previous reports, suggesting that the therapeutic effect may be achieved by an alternative mechanism(s) rather than by systemic elevation of IL-1Ra. These observations provide the first evidence that direct intramuscular injection of expression plasmid for IL-1Ra may effectively suppress the inflammatory pathology in arthritis.

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“…There has been considerable progress in defining the essential functions oflL-1 in vivo by using either neutralizing monoclonal antibodies (against IL-1 or against the IL-1 receptors) (14)(15)(16), soluble IL-1 receptors (17), or the naturally occurring IL-1 receptor antagonist (IL-lra) (18) to block IL-1 action in experimental animal models. Using these approaches, IL-1 has been implicated as a significant mediator in the generation of fever (19) and acute inflammatory responses (20).…”

mentioning

confidence: 99%

Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone.

Shornick

Togni

Mariathasan

et al. 1996

The Journal of Experimental Medicine

228

133

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SummaryMice rendered deficient in IL-1[3 by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-l~-deficient mice showed normal synthesis and cellular release of IL-lct after treatment with 5 mM ATP demonstrating that IL-113 is not necessary for expression and release of the IL-lot isoform. Mice deficient in IL-I~ showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL-lJ3-deficient mice showed defective contact hypersensitivity responses to topically applied trinitrochlorobenzene (TNCB). This defect could be overcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1[3 immediately before antigen application. These data demonstrate an essential role for IL-1[3 in contact hypersensitivity and suggest that IL-1{3 acts early during the sensitization phase of the response. They suggest an important role for 1I.-1(3 in initiation of the host response at the epidermal barrier.

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Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist

Cited by 1,040 publications

References 43 publications

Interleukin-10 and Interleukin-1 receptor antagonists increase during cardiac surgery

Interleukin-10 and Interleukin-1 receptor antagonists increase during cardiac surgery

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone.

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