title: A Comparison of the Anti-Inflammatory Effects of Cis-9, Trans-11 Conjugated Linoleic Acid to Celecoxib in the Collagen-Induced Arthritis Model.
abstract: Cyclooxygenase (COX)-2 inhibitors, such as celecoxib, for chronic inflammatory disease are associated with adverse health events, while cis-9, trans-11 (c9t11) conjugated linoleic acid (CLA) is anti-inflammatory without adverse events attributed to pure intake. Mechanistically, celecoxib and c9t11 disrupt the arachidonic acid cascade; however, the equivalency of anti-inflammatory effects between these compounds is unknown. Therefore, to test the hypothesis that 0.5% dietary c9t11 reduces inflammation equivalently to a celecoxib dose intended to treat rheumatoid arthritis (RA; 5 mg/kg bw), arthritic mice received diets containing one of the following supplements: 1% corn oil (CO, w/w), 0.5% c9t11 (>91% purity) +0.5% CO, or 1% CO + 0.5, 5, or 50 mg/kg bw celecoxib, and were assessed for changes in arthritic severity over 6 weeks. Overall, arthritic severity in mice fed c9t11 was reduced (34%, P < 0.01) while celecoxib doses (0.5, 5, 50 mg/kg) reduced arthritic severity (16, 56, 48%, respectively) compared to CO-fed arthritic mice. Linear regression of the celecoxib dose-response showed 0.5% c9t11 (570 mg/kg bw) reduced arthritic severity equivalently to 1.5 mg/kg celecoxib. Interleukin-6 (IL-6) was increased in paws of arthritic mice fed CO compared to shams, but was decreased in arthritic groups fed 0.5% c9t11 and 5 mg/kg celecoxib, compared to arthritic mice fed CO (Ps ≤ 0.05). Additionally, paw and plasma IL-10 levels in arthritic mice were decreased by 5 mg/kg celecoxib, but were unaffected by c9t11 compared to CO. Results suggest dietary c9t11 may be an effective adjunct to COX-2 inhibition for treating chronic inflammation.
authors.affiliation: Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Jake M
authors.initials: JM
authors.lastname: Olson
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Haas
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lor
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Holly S
authors.initials: HS
authors.lastname: McKee
authors.affiliation: Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI, 53706, USA. mcook@wisc.edu.|Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA. mcook@wisc.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cook
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D000068579:Celecoxib / Q000008:administration & dosage* / Q000494:pharmacology; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016014:Linear Models; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D044243:Linoleic Acids, Conjugated; C503589:cis-9, trans-11-conjugated linoleic acid; D016753:Interleukin-10; D000068579:Celecoxib
keywords: COX inhibitor; Celecoxib; Collagen-induced arthritis; Conjugated linoleic acid; Cyclooxygenase; Inflammation