Effects of interleukin-1 receptor antagonist on collagen and matrix metalloproteinases in stress-shielded achilles tendons of rats

Abstract

Based on previous studies showing that interleukin-1 (IL-1) significantly increased after stress shielding, this article reports further research into the possible therapeutic applications of IL-1 receptor antagonist (IL-1Ra). Forty rats whose left Achilles tendons were denervated and completely stress shielded were divided into 5 groups: 2-week phosphate-buffered saline (PBS); 4-week PBS; 2-week IL-1Ra; 4-week IL-1Ra; and normal control. The Achilles tendons were tested morphologically, and the changes in collagen I and III, matrix metalloproteinases (MMP)-1 and -3, and tissue inhibitors of metalloproteinase (TIMP)-1 were determined. The collagen fibrils in the IL-1Ra groups were morphologically more similar to those in the control group than to those in the PBS groups. The collagen I levels increased in the 2-week groups. Significant differences existed between the PBS and IL-1Ra groups at 4 weeks. The MMP-1 level increased dramatically after stress shielding and increased less in the 2-week IL-1Ra group than in the 2-week PBS group. The degree of decrease of MMP-3 in the IL-1Ra groups was significantly less than that in the PBS groups. The collagen III and TIMP-1 levels continued to increase, and no difference was found between the PBS and IL-1Ra groups. Interleukin-1 receptor antagonist prevented morphological deterioration and collagen metabolism of the denervated Achilles tendons after stress shielding, likely by inhibiting the decline of MMP-3 and increasing MMP-1 levels at an early stage.