Original article
Inflammatory Cytokine Profiles Associated With Chondral Damage in the Anterior Cruciate Ligament–Deficient Knee

https://doi.org/10.1016/j.arthro.2005.08.034Get rights and content

Purpose: Patients with chronic anterior cruciate ligament (ACL) deficiency are at high risk of articular cartilage damage and the development of osteoarthritis (OA). It has been hypothesized that biochemical factors, such as cytokines, contribute to the process. The purpose of our study was to determine the concentrations of potentially chondrodestructive and chondroprotective cytokines in the chronic ACL-deficient knee, and to determine if the cytokine profile or other factors correlated with the amount of chondral damage present in the knee. Type of Study: A consecutive series of patients who consented to the Institutional Review Board–approved study. Methods: Synovial fluid lavages were obtained from 31 patients with ACL-deficient knees. Four patients had lavages aspirated from their contralateral normal knee. These lavages were analyzed for interleukin (IL)-1α, IL-1β, IL-1ra, and tumor necrosis factor (TNF)-α. At arthroscopy, the amount of chondral damage was graded based on the Outerbridge classification. Results: Concentrations of chondrodestructive IL-1β and TNF-α were significantly higher in patients with ACL ruptures than in the contralateral normal knees. The more severe the chondral damage, the higher the concentration of IL-1β and TNF-α. Chondroprotective cytokine concentrations decreased with increasing grades of chondral damage. We found a linear correlation between the severity of chondral damage and the time from injury (r2 = .954). Conclusions: A difference was seen in the cytokine profiles between the normal and injured knees. This difference varied based on the severity of chondral damage, which was associated with time from injury. Clinical Relevance: Cytokine levels are associated with chondral damage.

Section snippets

Methods

This study included a consecutive series of patients who met the study inclusion criteria. Patients had to be between the age of 18 and 45 years and sign an Institutional Review Board–approved consent form. All patients had a diagnosed ACL tear on clinical examination that was verified at arthroscopy in order to complete the enrollment. Patients were excluded from the study if meniscal pathology or other ligament pathology was identified at arthroscopy. All patients were surveyed regarding date

Articular Surface Grading

Two patients were grade 0 with intact articular surfaces and no signs of pathology. Eight patients were Outerbridge grade I with softening of the articular surface. Seven patients had partial-thickness defects less than 1.5 cm and were graded Outerbridge II. Twelve patients were grade III with partial-thickness defects greater than 1.5 cm, and 2 patients had full-thickness defects down to bone and were classified as Outerbridge IV.

Chondral Damage Versus Time From Index ACL Injury

For patients with grade 0 chondral damage, the mean time from

Discussion

To better understand the natural history of cartilage loss in the ACL-deficient knee, this study measured cytokine levels in the chronic ACL-deficient knee. Our results showed that the concentrations of chondrodestructive cytokine, IL-1β, and TNF-α were elevated in injured knees. The level of chondroprotective IL-1ra also increased; however, the increase was much less than the corresponding increases in chondrodestructive cytokines. Differences in cytokine concentrations were also seen based on

Conclusions

In this study, we found an elevation of both chondrodestructive and chondroprotective cytokines in the ACL-deficient knee. Chondrodestructive cytokines are more markedly increased than their inhibitors. This suggests a possible imbalance between cartilage-damaging and cartilage-preserving factors in favor of the cartilage-damaging cytokines. This imbalance may result in progressive cartilage loss over time. Continued work in this area may identify disease-modulating cytokines that may be able

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