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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • January 31, 2015

Published In

Volume / Issue

  • 29 /

Start / End Page

  • 124 - 139

PubMed ID

  • 25636786

Pubmed Central ID

  • 25636786

Electronic International Standard Serial Number (EISSN)

  • 1473-2262

International Standard Serial Number (ISSN)

  • 1473-2262

Language

  • eng