The use of an IL1-receptor antagonist to reverse the changes associated with established tendinopathy in a rat model

Abstract

Interleukin-1 (IL1) is a cytokine that plays a role in inflammation and is a potential contributor to the inflammation present in tendinopathy. Its inhibition may be of use in the treatment of tendinopathy and has been a target for treatment. To evaluate how an IL1-receptor antagonist (IL1-RA) reverses pathologic changes associated with established patellar tendinopathy, we randomized 48 Sprague-Dawley retired breeder rats into three groups having weekly bilateral patellar tendon injections for 6 weeks. The control group received 0.1 mL saline for 6 weeks. The intervention groups were treated with 0.1 mL 2% carrageenan for 4 weeks. Beginning at week three, the IL1-RA group received 0.94 mg of the IL1-RA (2.5 mg/kg) added to the 0.1 mL 2% carrageenan and 0.94 mg of the IL1-RA alone for the final 2 weeks, while the CAR received 0.1 mL saline for the final 2 weeks. Animals were euthanized 6 weeks after initial injection. The CAR group demonstrated significantly (P < 0.05) shorter tendon lengths (7.81 ± 0.44 mm) than the control (8.25 ± 0.58 mm) and IL1-RA (8.34 ± 0.52 mm) group (P < 0.05). Macroscopically, plaque-like formations were reduced and margins of the tendon were more evident in the IL1-RA group compared to the CAR group. CAR group demonstrated significantly greater histopathologic changes (inflammatory cell density, disorganization of collagen, nuclear rounding, and angiogenesis) than the control and IL1-RA group. No significant difference in mechanical properties of the tendon was noted. These findings demonstrate IL1-RA can reduce pathologic changes in the patellar tendon in an established tendonitis model although did not demonstrate a difference in mechanical properties.