Injecting Anti-Inflammatories into Knee After Injury Aids Porcine Healing

DURHAM, N.C., Aug 30 -- Systemic anti-inflammatory agents injected directly into injured or arthritic knees may aid natural repair, according to a study in pigs.

When agents that block inflammatory cytokines were delivered into cultured porcine explants, meniscus healing began, Farshid Guilak, Ph.D., of Duke University here, and colleagues, reported in the September issue of Arthritis & Rheumatism.

The inhibitors of the proinflammatory cytokines were the IL-1 receptor antagonist (IL-1Ra) or anakinra (Kineret) and the anti-TNF monoclonal antibody infliximab (Remicade), which binds TNF-?, or the soluble TNF-? receptor etanercept (Enbrel).

In the in-vitro study, explants (8 mm in diameter) were harvested from the medial menisci of mature female pigs.

To simulate a full-thickness defect, a 4-mm-diameter core was removed and reinserted. Explants were cultured for 14, 28, or 42 days in the presence of 0-1,000 pg/mL of IL-1 or TNF.

Explants were also cultured in the presence of IL-1 or TNF with IL-1 receptor antagonist (IL-1Ra) or TNF monoclonal antibody (mAb).

At the end of the culture period, biomechanical testing, cell viability, and histologic analyses were done to quantify the extent of repair.

In control explants, mechanical testing revealed increased repair strength, cell accumulation, and tissue formation at the interface over time under control conditions.

Pathophysiologic concentrations of both IL-1 and TNF-? significantly decreased repair strength, cell migration, and tissue formation at the interface compared with controls. The inhibitory effect was present even at the lowest concentration of IL-1, which significantly decreased the extent of repair at all points (P

This in vitro model provides a quantitative means of studying the influence of specific pharmacologic inhibitors and their mechanisms of action on integrative repair of the meniscus, they concluded.