A mechanistic approach to understanding conjugated linoleic acid's role in inflammation using murine models of rheumatoid arthritis.
A naturally occurring fatty acid, conjugated linoleic acid (CLA), reduces immune-induced TNF and inducible cyclooxygenase (COX-2) expression; key mediators of inflammation in rheumatoid arthritis (RA). On the basis of previous work, it was hypothesized that dietary CLA would act as an anti-inflammatory agent in select animal models of RA. In the collagen antibody-induced arthritis (CAIA) model, mice fed CLA (mixed isomers of c9, t11, and t10, c12-CLA) for 3 wk before anticollagen antibody injection had reduced lipopolysaccharide-induced plasma TNF levels and had arthritic scores that were 60% of mice fed corn oil (CO). In the collagen-induced arthritis (CIA) model, mice fed mixed isomers of CLA for 21 days before immunization had lower IgG(1) titers, earlier signs of joint inflammation, but similar arthritis scores compared with CO fed mice during the remaining 70-day post-injection period. Beginning on day 80 to 133, CLA-fed mice had arthritic scores 70% that of the CO-fed mice. In a second CIA experiment, CLA was fed only after the booster injection. Plasma IgG(1) levels were not reduced and arthritis onset was delayed 4 days in CLA-fed mice compared with the CO-fed mice. Peak arthritis score was similar between CLA and CO-fed mice from day 35 to 56. Because CLA reduced inflammation in the CAIA model, delayed onset of arthritis in the CIA model (CIA experiment 2) and reduced arthritis score after day 80 in the CIA model (CIA experiment 1), we concluded that dietary CLA exhibited anti-inflammatory activity that was dependent on antibody.
Butz
Daniel E
DE
Nutritional Sciences, University of Wisconsin-Madison, 1675 Observatory Dr., Madison, WI 53706, USA.
Li
Guangming
G
Huebner
Shane M
SM
Cook
Mark E
ME
D000821:Animal Feed; D000818:Animals; D001169:Arthritis, Experimental / Q000178:diet therapy / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000178:diet therapy* / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004041:Dietary Fats / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D044243:Linoleic Acids, Conjugated / Q000276:immunology* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001323:Autoantibodies; D004041:Dietary Fats; D007074:Immunoglobulin G; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2