Inhibition of IL6 Receptor Improves Arthritis and Atherosclerosis in a Mouse Model of Rheumatoid Arthritis

Amy Archer¹, Carla Cuda², Alexander Shaffer², Emily Alex Waters³, Chad Haney⁴, Rana Saber², George Kenneth Haines III⁵, Jason Low⁶ and Harris R. Perlman⁷, ¹Rheumatology, Northwestern University, Chicago, IL, ²Northwestern University, Chicago, IL, ³Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, ⁴Center for Advanced Molecular Imaging, Northwestern University, Evanston, IL, ⁵Mount Sinai, New York, NY, ⁶Genentech, San Francisco, CA, ⁷Feinberg School of Medicine, Northwestern University, Chicago, IL

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: Atherosclerosis and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Animal Models Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Rheumatoid arthritis is a chronic, systemic, autoimmune disease associated with an increased risk of cardiovascular disease. However, it is unclear what role patients’ dyslipidemia plays in enhancing this cardiovascular risk. Moreover, the impact that treatments for rheumatoid arthritis have on both dyslipidemia and cardiovascular disease is under investigation. Anti-IL6 receptor (aIL6R) therapy is an effective treatment for rheumatoid arthritis but can be associated with an unfavorable lipid profile. Our study examines whether treatment with aIL6R is able to improve both inflammatory arthritis and early atherosclerosis in a mouse model of rheumatoid arthritis (K/BxA^g7).

Methods: K/BxA^g7mice on a high fat diet were treated with a murine aIL6R monoclonal antibody (cMR16-1) three times a week for 12 weeks. Arthritis was histologically assessed by a blinded pathologist and with SPECT/CT. Atherosclerosis was determined with whole mount sudan IV staining, sections though the aortic root and MRI. Serum cholesterol levels and cytokine levels were determined via enzymatic and luminex assays respectively.

Results: Our data show that cMR16-1 improves both articular and extra-articular inflammation, but does not influence bone resorption. In addition, sudan IV staining showed a decrease in the area of early atherosclerosis by 30%. As expected there was an associated increase in serum IL6. We also observed an increase in adiponectin, leptin, VEGF and RANTES, as well as a decrease in GRO-alpha. However, in our model treatment with cMR16-1 was not associated with any changes in the lipid profile of the K/BxA^g7mice.

Conclusion: Thus our data suggest that cMR16-1 is able to improve arthritis and early atherosclerosis in the absence of changes to the lipid profile in our mouse model of rheumatoid arthritis. This suggests that changes to the standard lipid profile may not be the ideal parameter to monitor in assessing the ability of treatments for rheumatoid arthritis to improve atherosclerosis.

Disclosure: A. Archer, None; C. Cuda, None; A. Shaffer, None; E. A. Waters, None; C. Haney, None; R. Saber, None; G. K. Haines III, None; J. Low, Genentech and Biogen IDEC Inc., 3; H. R. Perlman, None.

To cite this abstract in AMA style:

Archer A, Cuda C, Shaffer A, Waters EA, Haney C, Saber R, Haines GK III, Low J, Perlman HR. Inhibition of IL6 Receptor Improves Arthritis and Atherosclerosis in a Mouse Model of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/inhibition-of-il6-receptor-improves-arthritis-and-atherosclerosis-in-a-mouse-model-of-rheumatoid-arthritis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/inhibition-of-il6-receptor-improves-arthritis-and-atherosclerosis-in-a-mouse-model-of-rheumatoid-arthritis/