ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 934

Amelioration of Inflammatory Arthritis By Anti-TNF Therapy Is Associated with Restoration of Lymphatic Contraction

Echoe M. Bouta1, Igor Kuzin2, Karen de Mesy-Bentley1, Ronald Wood3, Homaira Rahimi4, Rui-Cheng Ji5, Christopher T. Ritchlin6, Andrea Bottaro2, Lianping Xing7 and Edward M. Schwarz8, 1University of Rochester, Rochester, NY, 2Cooper Medical School, Camden, NJ, 3Department of Urology, University of Rochester Medical Center, Rochester, NY, 4Rheumatology, University of Rochester/Golisano Children's Hospit, Rochester, NY, 5Department of Anatomy, Biology and Medicine, Oita University, Oita, Japan, 6Allergy Immunology & Rheumatology, University of Rochester Medical Center, Rochester, NY, 7Pathology & Lab Medicine, University of Rochester, Rochester, NY, 8Center for Musculoskeletal Research, University of Rochester, Rochester, NY

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Animal models, anti-TNF therapy, Lymph node, monocytes and rheumatoid arthritis

  • Tweet
  • Email
  • Print
Session Information

Session Title: Rheumatoid Arthritis - Animal Models I

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with episodic flares. In tumor necrosis factor transgenic (TNF-Tg) mice, a model of inflammatory-erosive arthritis, the popliteal lymph node (PLN) enlarges during the pre-arthritic “expanding” phase, and then “collapses” with adjacent knee flare associated with the loss of the intrinsic lymphatic pulse. Thus, a critical question is whether loss of the lymphatic pulse can be recovered by standard RA therapies.

Methods: We tested the hypothesis that anti-TNF vs. irrelevant IgG (IgG); and methotrexate (MTX) vs. saline treatment ameliorates knee synovitis adjacent to collapsed PLN in TNF-Tg mice by restoring the lymphatic pulse using contrast enhancement MRI (CE-MRI), ultrasound, near infrared indocyanine green (NIR-ICG) imaging, transmission electron microscopy (TEM) and flow cytometry.

Results: Anti-TNF treatment significantly decreased normalized synovial volume compared to IgG (0.87±0.21 vs. 1.52±0.16; p<0.05), measured by CE-MRI. This decrease correlated with a lower power Doppler volume within the joint, a measure of inflammation, in both anti-TNF and MTX treated mice compared to placebo treated (0.04±0.01 vs. 0.20±0.03 mm3 and 0.05±0.01 vs. 0.18±0.08 mm3, respectively; p<0.05). Lymphatic pulse rate and clearance were measured via NIR-ICG imaging (Figure). As predicted, anti-TNF significantly increased the lymphatic pulse vs. IgG (2.63±0.68 vs. 0.99±0.36 pulses/min), and MTX also induced an increase vs. saline (1.38±0.21 vs. 0.38±0.38 pulses/min), although this effect was weaker than anti-TNF. Consistently, footpad clearance of ICG was higher in anti-TNF and MTX treated mice vs. placebos (64.53±6.08 vs. 30.84±12.26 and 64.54±6.20 vs. 42.49±5.69, respectively; p<0.05). To gain insight into the mechanism of lymphatic pulse restoration, TEM was performed on the lymphatic vessels. We found that placebo treated mice showed damaged lymphatic endothelial cells (LECs) and smooth muscle cells (LSMCs), while anti-TNF treated mice showed intact LECs and LSMCs apical to fibrotic tissue, suggestive of tissue repair. Interestingly, anti-TNF treatment resulted in a significant ~4-fold increase in monocyte numbers normalized to placebo vs. MTX (3.77±0.77 vs. 1.08±0.19 cells per PLN; p<0.05), via flow cytometry. We previously reported monocytes trafficking in afferent lymphatic vessels. Thus, these findings indicate increased transit of monocytes to the PLN from the inflamed joint.

Conclusion: These NIR-ICG, CE-MRI and flow cytometry results demonstrate that anti-TNF increases lymphatic transport to a greater extent than MTX. Furthermore, our data suggest that the primary mechanism for monocyte (type 1 synoviocyte) removal from inflamed joints following anti-TNF treatment is through restoration of lymphatic pulse and cellular egress.

Description: Description: ICG.png


Disclosure:

E. M. Bouta,
None;

I. Kuzin,
None;

K. de Mesy-Bentley,
None;

R. Wood,
None;

H. Rahimi,
None;

R. C. Ji,
None;

C. T. Ritchlin,

Eli Lilly and Company,

9,

Eli Lilly and Company,

5;

A. Bottaro,
None;

L. Xing,
None;

E. M. Schwarz,

Johnson & Johnson,

5,

NIAMS-NIH,

2.

  • Tweet
  • Email
  • Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/amelioration-of-inflammatory-arthritis-by-anti-tnf-therapy-is-associated-with-restoration-of-lymphatic-contraction/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies