Cytokine status in posttraumatic synovitis on the background of systemic and intra-articular use of NSAID and ozone

Abstract

Joint damage initiates aseptic self-sustaining inflammation, which contributes the progression of post-traumatic destruction of tissues not only in the pathological focus, but also outside it, significantly expanding the zone of degenerative changes due to secondary alterations. One of the leading roles in pathogenesis of the inflammation belongs to secreted mediators-cytokines – that impart to the cells the proinflammatory potential and promote the long-term inflammation. These effects lead to disorganization of extracellular matrix and progressive disintegration of cartilage. In this regard, the development and implementation of new pathogenetic treatment methods of post-traumatic synovitis permits to limit the area of secondary alterations and activate reparative mechanisms in the lesion from the early terms, thus potentially improving the results of rehabilitation treatment and increasing efficiency of conventional therapy in post-traumatic synovitis. Numerous experimental and clinical studies have proven the effectiveness and safety of ozone therapy, e.g., in degenerative joint diseases. Despite extensive data highlighting effectiveness of ozone therapy in articular pathology, the study of cytokine profile when using this treatment of posttraumatic synovitis was performed only in few works, thus emphasizing the prospects for further research in this direction. The study was aimed for investigation of cytokine status in the patients with posttraumatic synovitis subjected to intravenous and intraarticular ozone therapy in combination with intra-articular administration of xefocam. The work is based on the results of examination and treatment of 69 patients with traumatic injuries of the knee joint, complicated by development of post-traumatic synovitis. Two study groups were formed, comparable in volume and type of joint injury. The patients from group I (35 cases) received conventional combined treatment. Among the mandatory measures, evacuation of a synovial-hemorrhagic punctate was performed from the cavity of damaged joint. Conservative therapy included NSAIDs, medications that improve microcirculation, at standard dosages, as well as physical therapy. In group II (34 patients), traditional therapy was supplemented with a 10-day course of intravenous injectable ozone therapy with 200 ml of NaCl solution at a concentration of 2.0 mg/l daily and intra-articular ozone injection at a concentration of 5 mg/l in a volume of 20 ml 5 times in a day. During arthroscopy, lavage of the joint cavity was performed with ozonated saline solution at a concentration of 2.0 mg/l. The ozone therapy was combined with three intra-articular injections of xefocam at a dose of 8 mg, once every 4 days. A patent for the invention was obtained for this treatment technology (No. 2456988 of 27.07.12). The cytokine profile was evaluated by the content of Pro-inflammatory (TNFα, IL-1β, IL-6, IL-17), regulatory (IL-2), Il-1β receptor antagonist, and anti-inflammatory (IL-4, IL-10) cytokines by solid-phase enzyme immunoassay with an indicator label in the form of peroxidase. Statistical analysis of the results was carried out using the Student criterion. Combined therapy of intravenous and intraarticular ozone therapy in combination with intra-articular injections of xefocam contributed to the inhibition of the inflammatory response, which is reflected in the dynamics of depression of the studied cytokines: simultaneous reduction of proinflammatory cytokines with the limitation of the growth of anti-inflammatory mediators. The final measurements showed a decrease in the content of proinflammatory cytokines: TNFα by 24.6% (p 2 < 0.001); IL-17, by 17.3% (p 2 < 0.01); IL-6, by 20.1% (p 2 < 0.001); IL-1β, by 19.1% (p 2 < 0.001), with a decrease in regulatory IL-2 by 25.7% (p 2 < 0.001) and anti-inflammatory cytokines IL–10, by 21.3% (p 2 < 0.001); Il – 4, by 25.7% (p 2 < 0.001); IL-1ra, by 24.4% (p 2 < 0.001), when compared to the data obtained with conventional treatment. The results obtained allow us to evaluate this method as highly effective in the treatment of post-traumatic synovitis, thus contributing to suppression of inflammatory response and reduces the secondary alteration of joint tissue structures, preventing the progression of post-traumatic osteoarthritis.