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Conjugated linoleic acid reduces inflammation in animal models: Evidence of a molecular mechanism

Posted on:2006-03-03Degree:Ph.DType:Dissertation
University:The University of Wisconsin - MadisonCandidate:Butz, Daniel EFull Text:PDF
GTID:1454390008957770Subject:Health Sciences
Abstract/Summary:
Rheumatoid arthritis (RA) is a debilitating autoimmune condition resulting in severe inflammation in articular joints. Inflammation is dependant on pro-inflammatory cytokines (i.e. tumor necrosis factor, TNF) and cyclooxygenase (COX) derived eicosanoids. Dietary conjugated linoleic acid (CLA) has been shown to reduce plasma TNF and COX derived eicosanoids after an immune stimulus.; We hypothesized that dietary CLA is anti-inflammatory in the collagen induced arthritis (CIA) model of RA. In this model, dietary CLA90 (1:1 mix of c9, t11 and t10, c12 CLA isomers) did not reduce or increase inflammation during the initial 80 days after immunization. From days 100 to 133 mice fed CLA90 may have reduced inflammation. Dietary CLA90 reduced plasma total anti-CII IgG, and anti-IgG1. In the anti-collagen antibody induced arthritis (CAIA) model, mice fed CLA90 had clinical scores that were 60% of the corn oil (CO) fed mice. Dietary CLA90 reduced plasma TNF concentration compared to CO fed mice 1 hour after LPS injection.; To examine the isomer specific effect of dietary CLA we used the LPS induced weight loss model. All mice lost weight 24 hours after LPS injection, and neither c9, t11 nor t10, c12 CLA isomer prevented immune induced weight loss. However, t10, c12 CLA fed mice regained weight significantly faster than did the c9, t11 CLA or olive oil fed mice. In a second study, it was confirmed that neither isomer protected immune induced weight loss 24 hours after LPS injection to the extent of CLA90 feeding, and dietary t10, c12 CLA causes compensatory gain. Both t10, c12 CLA and CLA90 reduced plasma TNF concentration 2 hours after LPS injection.; In a similar study mice were fed c9, t11, t10, c12 CLA or CO, and lung tissue was harvested. Dietary t10, c12 reduced COX-2 expression and PGE 2 production in the lung. Cells supplemented with t10, c12 CLA have reduced COX-2 expression and express less inducible nitric oxide and COX-2 mRNA after LPS stimulation. Neither t10, c12 CLA nor LA reduced total IkappaB, but t10, c12 CLA reduced phosphorylated-IkappaB. These data indicate that t10, c12 CLA may have anti-inflammatory actions.
Keywords/Search Tags:C12 CLA, Hours after LPS injection, Inflammation, T10, Plasma TNF, Model, Induced weight loss, Fed mice
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