eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2015   Volume No 29 – pages 124-140

Title: Sustained intra-articular delivery of IL-1Ra from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis

Author: KA Kimmerling, BD Furman, DS Mangiapani, MA Moverman, SM Sinclair, JL Huebner, A Chilkoti, VB Kraus, LA Setton, F Guilak, SA Olson

Address: Duke University Medical Center, Box 3389, Durham, NC 27710, USA

E-mail: olson016 at mc.duke.edu

Key Words: Arthritis, murine model, cartilage, drug delivery, inflammation.

Publication date: January 31st 2015

Abstract: Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.

Article download: Pages 124-140 (PDF file)
DOI: 10.22203/eCM.v029a10