Linked Life Data

8759766

Source:http://linkedlifedata.com/resource/pubmed/id/8759766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-9-17
pubmed:abstractText
We have used fas-defective MRL-lpr/lpr mice to study the effects of the staphylococcal enterotoxin superantigens on the development of autoimmune, inflammatory joint disease in animals that are susceptible to the development of rheumatoid arthritis-like disease. We show that systematic administration by a single i.p. injection of staphylococcal enterotoxin B (SEB; 10 micrograms/mouse) caused a mild, inflammatory arthritis +30 days postchallenge in the knee joints of young (< 2-mo-old) MRL-lpr/lpr mice, but not aged-matched MRL +/+ mice. In aged (> 8-mo-old) MRL-lpr/lpr mice, but not in aged MRL +/+ mice, SEB caused a severe, inflammatory arthritis, as assessed histologically, and systemic autoimmune disease, including glomerulonephritis and autoantibody production. Furthermore, in aged MRL-lpr/lpr mice, SEB but not heat-denatured SEB caused acute weight loss and elevated levels of serum proinflammatory cytokines. Compared with highly purified peritoneal macrophages obtained from either aged MRL +/+, young MRL-lpr/lpr, or young MRL +/+, peritoneal macrophages obtained from aged MRL-lpr/lpr mice constitutively expressed 2- to 10-fold greater levels of TNF-alpha, IL-1 beta, IL-6, and IL-10, and produced elevated amounts of these cytokines when treated in vitro with SEB. SEB-challenged aged MRL-lpr/lpr mice treated with anti-TNF mAb (100 micrograms/mouse; every other day), anti-V beta 8 TCR mAb (250 micrograms/mouse; every other day), or orally with the novel TNF-alpha inhibitor MDL 201,449A (9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine; 25 mg/kg/day) exhibited reduced inflammatory arthritis, autoantibody formation, and serum TNF-alpha levels, but not IL-10 levels, after +30 days of treatment. These data suggest that SEB is an extremely potent macrophage-activating factor in vitro and in vivo, enhancing several aspects of autoimmune disease in MRL-lpr/lpr mice, and that anti-TNF therapies may have potential use in inflammatory arthritis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
157
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1758-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8759766-Aging, pubmed-meshheading:8759766-Animals, pubmed-meshheading:8759766-Antibodies, Monoclonal, pubmed-meshheading:8759766-Antigens, Bacterial, pubmed-meshheading:8759766-Antigens, CD95, pubmed-meshheading:8759766-Arthritis, Infectious, pubmed-meshheading:8759766-Autoimmune Diseases, pubmed-meshheading:8759766-Cells, Cultured, pubmed-meshheading:8759766-Cytokines, pubmed-meshheading:8759766-Enterotoxins, pubmed-meshheading:8759766-Glomerulonephritis, pubmed-meshheading:8759766-Histocompatibility Antigens Class II, pubmed-meshheading:8759766-Macrophages, Peritoneal, pubmed-meshheading:8759766-Mice, pubmed-meshheading:8759766-Mice, Mutant Strains, pubmed-meshheading:8759766-Protein Denaturation, pubmed-meshheading:8759766-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:8759766-Superantigens, pubmed-meshheading:8759766-Transcription, Genetic, pubmed-meshheading:8759766-Tumor Necrosis Factor-alpha
pubmed:year
1996
pubmed:articleTitle
Inhibition of superantigen-induced proinflammatory cytokine production and inflammatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF-alpha.
pubmed:affiliation
Department of Immunology, Hoechst Marion Roussel, Cincinnati, OH 45215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't