Local Administration Of Interleukin-1 Receptor Antagonist Intervening Achilles Tendon Contracture In Rats: A Empirical Study

ObjectiveTo understand the effects of interleukin-1 (IL-1) on tendon contracture and approach the interference effects and probable mechanisms of interleukin-1 receptor antagonist (IL1ra) on Achilles tendon (AT) contracture by investigating the morphological changes and the level of Type I and type III collagen, Transforming growth factor-β(TGF-β), matrix metalloproteinase-1 (MMP-1) and issue inhibitor of metalloproteinase-1 (TIMP-1) of the stress-shielded ATs in rats after the intervention of IL-1ra.MethodsThe animals comprised a total of 40 male SD rats, weighing 210±10g, age: 8-10 weeks. They are randomly divided into four groups, the 2-week PBS group, the 2-week IL-1ra group, the 4-week PBS group and the 4-week IL-1ra group. The normal control group (the fifth group) composed of the randomly ten right hindlimbs from the 2-week PBS group and the 2-week IL-1ra group. All the ATs of the left hindlimbs of rats were stress-shielded by fixing the upper ankle joint in equines position using a cerclage and transecting the sciatic nerve. Then they were raised in the cage where they could move about freely, received feed and water adlibitum, and given injection of penicillin in this duration for three days. The 2-week PBS group and the 2-week IL-1ra group were respectively injected 0.1mlPBS and 5μg rhIL-1ra/0.1mlPBS at day 0, 7. The 4-week PBS group and the 4-week IL-1ra group were respectively injected at day 0, 7, 14,21. The ATs of the left hindlimbs of the PBS groups and the IL-1ra groups were obtained 2 or 4 weeks later. The ATs of the right hindlimbs of the normal control group were obtained 2 weeks later. All the ATs were tested morphologically and biochemically.Results1. Morphologic changes:1) On gross examination, the ATs of the IL-1ra groups were significantly smoother and smaller than those of the PBS groups, but thicker than those of the normal-control group. 2) Under transmission electron microscope, the collagen fibrils of the 2-week PBS group and IL-1ra group were similar to those of the normal-control group in cross section, but looser and more disorder in longitudinal section. The collagen fibrils of the 4-week PBS group were significantly different to those of the normal-control group in longitudinal section and cross section, which were characterized by significantly increased small fibrils and disordered arrangement. The collagen fibrils of the 4-week IL-1ra group were approximate to those of the normal-control group in cross section, but slightly looser than those of the normal-control group in longitudinal section.2. Biochemical changes:The levels of typeⅠcollagen of the PBS group and the IL-1ra group were significantly increased when the ATs were stress-shielded for two weeks, but there was no significant difference between the two groups. Then it was significantly decreased at four weeks. That of the PBS group was lower than the normal level. That of the IL-1ra group was tended to be normal. The difference between the two groups was significant. The levels of type III collagen of the PBS group and the IL-1ra group were significantly increased at two weeks, but there was no significant difference between the two groups. Then it was significantly decreased at four weeks. The levels of TGF-βwere significantly increased at two and four weeks. There was no significant difference between the 2-week groups and the 4-week groups. The ratios of MMP-1/TIMP-1 of PBS group and the IL-1ra group were significantly increased, and that of the PBS group was significantly higher than that of the Il-1ra group at two weeks. The ratios of MMP-1/TIMP-1 at four weeks were tended to be normal, and there was no significant difference between the two groups.Conclusion1. IL-1 plays a critical role in tendon contracture, and IL-1ra can effectively intervene tendon contracture.2. The significantly increasing small fibrils were related to interleukin-1 in contracted tendon.3. The probable mechanisms of the interference effects of IL-1ra was decreasing the level of type collagen and increasing the ratio of MMP/TIMP.