Linked Life Data

11243513

Source:http://linkedlifedata.com/resource/pubmed/id/11243513

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-3-12
pubmed:abstractText
The CD154/CD40 pathway is required for the development and progression of disease in a variety of autoimmune model systems. We have demonstrated previously that long-term anti-CD154 treatment of nephritic (SWRxNZB)F1 mice prolonged survival and preserved kidney function. Herein we ask if long-term treatment is required and further characterize the protective effect on renal pathology by examining alpha-smooth muscle actin, collagen and TGF-beta1 expression in renal tissue. The effects of anti-CD154 on brain and heart inflammation are also examined. Three dosing strategies of anti-CD154 mAb were compared in SNF1 mice that exhibited moderate or severe nephritis: (1) weekly for 6 weeks; (2) monthly; (3) weekly for 6-12 weeks followed by monthly dosing. Proteinuria, serum anti-DNA, anti-CD154 pharmacokinetics and serum soluble CD154 analyses were performed. Anti-CD154 treatment of moderate disease increased survival across all regimens, although weekly followed by monthly maintenance dosing proved most efficacious. This regime also inhibited renal alpha-smooth muscle actin and collagen deposition. Only the most aggressive anti-CD154 treatment protocol increased survival in severely nephritic mice. Long-term anti-CD154 treatment significantly inhibits key mediators of kidney fibrosis and is required to maximize survival and renal function. Potential reasons for differential therapeutic efficacy in moderately vs severely nephritic mice are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0961-2033
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9-22
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Long-term anti-CD154 dosing in nephritic mice is required to maintain survival and inhibit mediators of renal fibrosis.
pubmed:affiliation
Department of Inflammation, Biogen Inc., Cambridge, Massachusetts 02142, USA. Susan_Kalled@Biogen.com
pubmed:publicationType
Journal Article