Cuellar Jason M, Scuderi Gaetano J, Cuellar Vanessa Gabrovsky, Golish S Raymond, Yeomans David C
Department of Orthopaedic Surgery, NYU-Hospital for Joint Diseases, 301 East 17th Street, New York, NY 10033, USA.
J Bone Joint Surg Am. 2009 Oct;91(10):2313-20. doi: 10.2106/JBJS.H.00835.
The diagnosis of clinically important meniscal tears of the knee remains challenging, and it is unknown why only some injuries become painful. The role of inflammatory cytokines in generating pain following meniscal injury remains unclear. This study aimed to investigate the cytokine profile in patients with acute knee pain believed to be secondary to meniscal damage.
This prospective cohort study included thirty-two patients without rheumatoid arthritis who had knee pain for less than six months, with either an acute or insidious onset, and elected to have arthroscopic treatment after nonoperative management had failed. Twenty-three of these patients elected to have the contralateral, nonoperatively treated knee lavaged at the time of arthroscopy. Fifteen asymptomatic control subjects also contributed samples of knee joint fluid, for a total of seventy samples from forty-seven subjects. Lavage of the operatively treated, contralateral, and control knees was performed with the patient under regional anesthesia prior to arthroscopy, if applicable, by the infusion of sterile saline solution into the knee followed by the immediate withdrawal into a syringe. The concentrations of seventeen inflammatory cytokines and chemokines were measured with use of a multiplexed immunoassay panel. Preoperative magnetic resonance imaging findings and cytokine assay results were compared with intraoperative findings.
Multivariate analysis of variance detected significantly greater concentrations of interferon gamma (IFN-gamma); interleukins 2, 4, 6, 10, and 13 (IL-2, IL-4, IL-6, IL-10, and IL-13); monocyte chemotactic protein-1 (MCP-1); and macrophage inflammatory protein-1 beta (MIP-1beta) in fluid samples from painful knees than in samples from nonpainful knees. Correlation analysis demonstrated a significant positive correlation between patient-reported pain scores and concentrations of IL-6 (Spearman rho = 0.7), MCP-1 (rho = 0.8), MIP-1beta (rho = 0.6), and IFN-gamma (rho = 0.6). These four cytokines also demonstrated a positive correlation with each other (rho = 0.5 to 0.7). The presence of IFN-gamma, IL-6, MCP-1, or MIP-1beta performed as well as magnetic resonance imaging in the prediction of intraoperative findings.
Intra-articular concentrations of four inflammatory cytokines IFN-gamma, IL-6, MCP-1, and MIP-1beta correlated to pain in patients with symptomatic meniscal tears in the knee but were markedly lower in asymptomatic normal knees and in asymptomatic knees with meniscal tears. These cytokines may be involved in the generation of pain following meniscal injury.
膝关节临床上重要的半月板撕裂的诊断仍然具有挑战性,并且尚不清楚为何只有部分损伤会引起疼痛。炎性细胞因子在半月板损伤后引发疼痛中的作用仍不明确。本研究旨在调查被认为继发于半月板损伤的急性膝关节疼痛患者的细胞因子谱。
这项前瞻性队列研究纳入了32例无类风湿关节炎的患者,这些患者膝关节疼痛少于6个月,起病急或隐匿,在非手术治疗失败后选择进行关节镜治疗。其中23例患者在关节镜检查时选择对侧未经手术治疗的膝关节进行灌洗。15名无症状对照者也提供了膝关节液样本,共来自47名受试者的70个样本。若适用,在关节镜检查前,在区域麻醉下对接受手术治疗的膝关节、对侧膝关节和对照膝关节进行灌洗,方法是向膝关节内注入无菌盐水溶液,然后立即抽回注射器。使用多重免疫分析板测量17种炎性细胞因子和趋化因子的浓度。将术前磁共振成像结果和细胞因子检测结果与术中发现进行比较。
多变量方差分析检测到,疼痛膝关节的液样中γ干扰素(IFN-γ)、白细胞介素2、4、6、10和13(IL-2、IL-4、IL-6、IL-10和IL-13)、单核细胞趋化蛋白-1(MCP-1)和巨噬细胞炎性蛋白-1β(MIP-1β)的浓度显著高于非疼痛膝关节的样本。相关性分析表明,患者报告的疼痛评分与IL-6(Spearman秩相关系数ρ = 0.7)、MCP-1(ρ = 0.8)、MIP-1β(ρ = 0.6)和IFN-γ(ρ = 0.6)的浓度之间存在显著正相关。这四种细胞因子之间也呈正相关(ρ = 0.5至0.7)。IFN-γ、IL-6、MCP-1或MIP-1β的存在在预测术中发现方面与磁共振成像表现相当。
四种炎性细胞因子IFN-γ、IL-6、MCP-1和MIP-1β的关节内浓度与有症状的膝关节半月板撕裂患者的疼痛相关,但在无症状的正常膝关节和有半月板撕裂的无症状膝关节中明显较低。这些细胞因子可能参与了半月板损伤后的疼痛产生。