Analysis of sequential cytokine release after ACL reconstruction

Hayward, Abigail; Deehan, David J.; Aspden, Richard M.; Sutherland, Alasdair

doi:10.1007/s00167-011-1486-0

Cited by 28 publications

(44 citation statements)

References 44 publications

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“…Few studies have reported on pre-and postoperative levels of synovial fluid cytokines after ACL reconstruction 13e15 . Two small studies (13 and 14 subjects, respectively) found increased levels of sfIL-6 in the immediate hours and days after ACL reconstruction compared to preoperative levels 13,15 . Conflicting data for sfTNF was reported with postoperative levels being both decreased and increased compared to preoperative levels, however, large variations in time between injury and ACL reconstruction may have influenced these results 14,15 .…”

Section: Discussionmentioning

confidence: 95%

“…Two small studies (13 and 14 subjects, respectively) found increased levels of sfIL-6 in the immediate hours and days after ACL reconstruction compared to preoperative levels 13,15 . Conflicting data for sfTNF was reported with postoperative levels being both decreased and increased compared to preoperative levels, however, large variations in time between injury and ACL reconstruction may have influenced these results 14,15 . Using an almost 10-fold larger study sample, we reported on longitudinal biomarker changes in the same cohort of ACL injured subjects as studied here but without accounting for treatment 7 .…”

Section: Discussionmentioning

confidence: 95%

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Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial

Larsson

Struglics

Lohmander

et al. 2017

Osteoarthritis and Cartilage

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial

Larsson

Struglics

Lohmander

et al. 2017

Osteoarthritis and Cartilage

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“…While increases in myostatin and TGF-β were anticipated and confirmed after ACL-R, of interesting note are several factors that did not demonstrate significantly different plasma levels after ACL reconstruction. IL-1α, IL-1β, IL-6 and TNF-α can directly cause muscle atrophy by activating proteolytic systems in muscle 20, 26, 27 , and levels of these cytokines increase in synovial fluid acutely following ACL tears 6, 10, 13, 23 . However, no differences in serum levels of IL-1α, IL-1β, IL-6, TNF-α or the IL-1 regulatory protein IL-1ra were detected at any time point in the current study.…”

Section: Discussionmentioning

confidence: 99%

Changes in Circulating Biomarkers of Muscle Atrophy, Inflammation, and Cartilage Turnover in Patients Undergoing Anterior Cruciate Ligament Reconstruction and Rehabilitation

et al. 2013

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Background Following ACL reconstruction, there is significant atrophy of quadriceps muscles which can limit full recovery and place athletes at risk for recurrent injury with return to play. The etiology of this muscle atrophy is not fully understood. Hypothesis We hypothesized that circulating levels of pro-atrophy, pro-inflammatory and cartilage turnover cytokines and biomarkers would increase following ACL reconstruction. Study Design Descriptive laboratory study. Methods Subjects (N=18, mean age 28±2.4 years) underwent surgical reconstruction of the ACL following non-contact athletic injury. Circulating levels of biomarkers were measured along with SF-12, IKDC and objective knee strength measures preoperatively, and at 6 postoperative visits. Differences were tested using repeated measures one-way ANOVA tests. Results Myostatin, TGF-β and CRP levels were significantly increased in the early postoperative period, and returned to baseline. COMP levels decreased immediately after surgery and then returned to baseline. CCL2, CCL3, CCL4, CCL5, EGF, FGF-2, IGF-1, IL-10, IL-1α, IL-1β, IL-1ra, IL-6, myoglobin and TNF-α were not different over the course of the study. Conclusions An increase in potent atrophy-inducing cytokines and corresponding changes in knee strength and functional scores were observed following ACL reconstruction. Clinical Relevance Although further studies are necessary, the therapeutic inhibition of myostatin may help prevent the muscle atrophy that occurs following ACL reconstruction and provide an accelerated return of patients to sport.

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“…10 Matrix metalloproteinase-3 (MMP-3) concentration, one of several enzymes involved in the signaling of cartilage matrix protein degradation, 16 is increased in knee synovial fluid as early as three weeks following ACL injury compared to uninjured controls. 17,18 Pro-inflammatory cytokine concentrations are increased following ACL injury as well as in the initial days following ACLR, [19][20][21] and are known to stimulate MMP production. 16 The addition of altered mechanical loading to injured joint tissues may further promote adverse changes to articular cartilage metabolism and hasten PTOA onset.…”

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confidence: 99%

Biochemical markers of cartilage metabolism are associated with walking biomechanics 6‐months following anterior cruciate ligament reconstruction

Pietrosimone

Loeser

Blackburn

et al. 2017

Journal Orthopaedic Research

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The purpose of our study was to determine the association between biomechanical outcomes of walking gait (peak vertical ground reaction force [vGRF], vGRF loading rate [vGRF-LR] and knee adduction moment [KAM]) six months following anterior cruciate ligament reconstruction (ACLR) and biochemical markers of serum type-II collagen turnover (collagen type-II cleavage product to collagen type-II C-propeptide [C2C:CPII]), plasma degenerative enzymes (matrix metalloproteinase-3 [MMP-3]), and a pro-inflammatory cytokine (interleukin-6 [IL-6]). Biochemical markers were evaluated within the first two weeks (6.5±3.8 days) following ACL injury and again six months following ACLR in eighteen participants. All peak biomechanical outcomes were extracted from the first 50% of the stance phase of walking gait during a six-month follow-up exam. Limb symmetry indices (LSI) were used to normalize the biomechanical outcomes in the ACLR limb to that of the contralateral limb (ACLR /contralateral). Bivariate correlations were used to assess associations between biomechanical and biochemical outcomes. Greater plasma MMP-3 concentrations after ACL injury and at the six-month follow-up exam were associated with lesser KAM LSI. Lesser KAM was associated with greater plasma IL-6 at the six-month follow-up exam. Similarly, lesser vGRF-LR LSI was associated with greater plasma MMP-3 concentrations at the six-month follow-up exam. Lesser peak vGRF LSI was associated with higher C2C:CPII after ACL injury, yet this association was not significant after accounting for walking speed. Therefore, lesser biomechanical loading in the ACLR limb, compared to the contralateral limb, six months following ACLR may be related to deleterious joint tissue metabolism that could influence future cartilage breakdown.

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Analysis of sequential cytokine release after ACL reconstruction

Abstract: These data support the contention that an anabolic response starts earlier than previously thought within the surgically reconstructed knee.

Cited by 28 publications

References 44 publications

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial

Changes in Circulating Biomarkers of Muscle Atrophy, Inflammation, and Cartilage Turnover in Patients Undergoing Anterior Cruciate Ligament Reconstruction and Rehabilitation

Biochemical markers of cartilage metabolism are associated with walking biomechanics 6‐months following anterior cruciate ligament reconstruction

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