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A Comparison of the Anti-Inflammatory Effects of Cis-9, Trans-11 Conjugated Linoleic Acid to Celecoxib in the Collagen-Induced Arthritis Model

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Lipids

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.

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Abbreviations

ARA:

Arachidonic acid

AUC:

Area under the curve

c9t11:

cis-9, trans-11

CA:

Collagen-induced arthritis

CAS:

Clinical arthritic score

CLA:

Conjugated linoleic acid

CO:

Corn oil

COX:

Cyclooxygenase

IL:

Interleukin

IMID:

Immune-mediated inflammatory disease

NF-κB:

Nuclear factor-kappa B

nsNSAID:

Nonselective non-steroidal anti-inflammatory drug

PG:

Prostaglandin

PLA:

Phospholipase

PPAR:

Peroxisome proliferator-activated receptor

TXA:

Thromboxane

TNF:

Tumor necrosis factor

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Acknowledgements

The authors express their gratitude toward Shane Huebner for technical assistance. The authors thank Dawn Irish, Angel Guterriez-Velin, and Terry Jobsis for their assistance with animal husbandry. The authors would like to thank Peter Crump for his assistance with statistical analyses. This research was partially supported by a USDA Hatch Project Grant (MSN130802), patent royalties from the Wisconsin Alumni Research Foundation (WARF), and the College of Agricultural and Life Sciences at the University of Wisconsin-Madison.

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Authors and Affiliations

  1. Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Jake M. Olson & Mark E. Cook

  2. Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Alexander W. Haas, Jennifer Lor, Holly S. McKee & Mark E. Cook

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  1. Jake M. Olson
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  2. Alexander W. Haas
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Correspondence to Mark E. Cook.

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This project was partially supported by a USDA Hatch project grants (MSN130802), patent royalties from the Wisconsin Alumni Research Foundation (WARF), and the College of Agricultural and Life Sciences at the University of Wisconsin-Madison.

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Olson, J.M., Haas, A.W., Lor, J. et al. A Comparison of the Anti-Inflammatory Effects of Cis-9, Trans-11 Conjugated Linoleic Acid to Celecoxib in the Collagen-Induced Arthritis Model. Lipids 52, 151–159 (2017). https://doi.org/10.1007/s11745-016-4228-8

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