Interleukin Expression after Injury and the Effects of Interleukin-1 Receptor Antagonist

Ligament and tendon repair involves a complex series of coordinated events orchestrated by various cell types, cytokines and other factors. The repair process extends months to years and results in scar tissue mechanically inferior to native tissue. This is in clear contrast to tissue regeneration which would recapitulate the native tissue. Numerous approaches to stimulate a regenerative scenario have been attempted, including tissue-engineering, non-steroidal anti-inflammatories, ultrasonic, or electrical stimulation, but none have resulted in complete regeneration. In pursuit of a more regenerative outcome, it is important to understand the fundamentals of the normal healing process. Previous work from our lab identified a number of cellular, vascular, and molecular components integral to early healing [1]-[3]. Specifically, macrophages within the injured ligament peaked between day 3 and 5, while blood vessels primarily appeared between day 7 and 11 post-injury. The change in macrophage infiltration and angiogenesis during healing is modulated by the interleukin environment. Macrophages provide an ongoing source of cytokines, including IL-1[alpha], IL-1[beta], IL-6, and TNF-[alpha], and are responsible for modulating inflammatory cell adhesion and migration as well as fibroblast proliferation. [4] Ablation of macrophage-produced cytokines subsequently results in decreased fibroblast proliferation and ECM deposition. Consequently, ablation of macrophageproduced cytokines impedes healing and delays functional recovery. [5] Therefore, identifying the interleukins specific to ligament injury during peak macrophage activation and angiogenesis may elucidate the inflammatory mechanisms and subsequent scar formation