Response to: cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection

Abstract

We welcome the interest of Rutgers and colleagues [1] in providing additional information on the mode of action of autologous conditioned serum (ACS). Studies such as the one they published in a recent issue of Arthritis Research & Th erapy are important because the Orthokine ACS treatment (Orthogen, Dusseldorf, Germany) has been shown to be safe and eff ective in a number of clinical studies and is used widely in Europe. Randomized controlled trials have confi rmed the effi cacy of this treatment in osteoarthritis of the knee and lumbar radiculopathy. Additional human studies show promise in treating muscle injury and tunnel widening after anterior cruciate ligament (ACL) reconstruction. All clinical and preclinical studies confi rm an excellent riskto-benefi t ratio. We would like to off er some comments concerning the paper of Rutgers and colleagues. Th e method of producing ACS has been carefully optimized to enrich for anti-infl ammatory cytokines, such as interleukin (IL)-1Ra, IL-10, and IL-13, while keeping low the concentration of infl ammatory cyto kines, such as IL-1β and tumor necrosis factor-alpha (TNF-α). Th e ACS preparation of Rutgers and colleagues had increased concen trations of IL-1β and TNF-α, and this raises questions about the composition of the product that was tested. Nevertheless, despite the elevated concentrations of these two cytokines, there was no adverse eff ect of ACS on proteoglycan turnover in the cartilage explant cultures. Th is suggests that anti-infl ammatory and possibly chondro protective ingredients within ACS pre dominate. Further studies using additional controls and autologous instead of heterologous serum would be interesting. Th e third component of the study by Rutgers and colleagues measured cytokine levels in synovial fl uids before and after treatment with ACS. No changes were found, but it should be noted that Orthokine should be used only when knee eff usion has been removed eff ectively. Th e described possible aspiration of synovial fl uid after treatment with ACS raises questions about the selection of these patients or the composition of the injected ACS. In this regard, it is worth noting that another study [2,3] involving the injection of Orthokine ACS into knees after ACL plasty showed evidence of reduced IL-1β content in synovial fl uid. Th is reduction corresponded with im proved pain and function and with reduced tunnel widening. Clearly, the mechanisms through which ACS brings about clinical improvement are incompletely understood and should be the subject of additional research.