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

K. A. Kimmerling, B. D. Furman, D. S. Mangiapani, M. A. Moverman, S. M. Sinclair, J. L. Huebner, A. Chilkoti, V. B. Kraus, L. A. Setton, F. Guilak, Steven A. Olson

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43 Scopus citations

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.

Original languageEnglish
Pages (from-to)124-140
Number of pages17
JournalEuropean Cells and Materials
Volume29
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Arthritis
  • Cartilage
  • Drug delivery
  • Inflammation
  • Murine model

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    Kimmerling, K. A., Furman, B. D., Mangiapani, D. S., Moverman, M. A., Sinclair, S. M., Huebner, J. L., Chilkoti, A., Kraus, V. B., Setton, L. A., Guilak, F., & Olson, S. A. (2015). Sustained intra-articular delivery of IL-1Ra from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. European Cells and Materials, 29, 124-140. https://doi.org/10.22203/eCM.v029a10