Jansen Nathalie W D, Roosendaal Goris, Hooiveld Michel J J, Bijlsma Johannes W J, van Roon Joël A G, Theobald Matthias, Lafeber Floris P J G
Rheumatology & Clinical Immunology, UMC Utrecht, The Netherlands.
Br J Haematol. 2008 Sep;142(6):953-61. doi: 10.1111/j.1365-2141.2008.07278.x. Epub 2008 Jul 8.
Despite prophylactic treatment, haemophilia patients suffer from spontaneous joint bleeds, which lead to severe joint damage. Also after joint trauma, an intra-articular haemorrhage can add to joint damage over time. This study evaluated interleukin 10 (IL-10) in the search for possible interventions to prevent or limit the damaging effects of joint bleeds. Human articular cartilage tissue explants were cultured in the presence or absence of 50% v/v blood (or its cellular components) for 4 d (the expected blood load in vivo after a joint haemorrhage), followed by a recovery period of 12 d. Pharmacological dosages of IL-10 reached during treatment (1 or 10 ng/ml) were added. Additionally, cartilage and synovial tissue obtained from joints with end-stage haemophilic arthropathy (HA) were cultured in the presence of IL-10 (10 ng/ml). IL-10 protected cartilage from the damaging effects of blood exposure, measured by its effects on proteoglycan turnover. In addition, IL-10 beneficially influenced cartilage from patients with HA and reduced the production of the inflammatory cytokines IL-1beta and tumour necrosis factor-alpha by haemophilic synovial tissue. Taken together, although effects were obtained in vitro, IL-10 protects against blood-induced joint damage and might be further evaluated as candidate in treatment of tissue damaging effects of joint haemorrhages.
尽管进行了预防性治疗,但血友病患者仍会出现自发性关节出血,这会导致严重的关节损伤。同样,在关节创伤后,随着时间的推移,关节内出血也会加重关节损伤。本研究评估了白细胞介素10(IL-10),以寻找可能的干预措施来预防或限制关节出血的破坏作用。将人关节软骨组织外植体在有或无50% v/v血液(或其细胞成分)的情况下培养4天(关节出血后体内预期的血液负荷),随后有12天的恢复期。添加治疗期间达到的药理学剂量的IL-10(1或10 ng/ml)。此外,将从终末期血友病性关节病(HA)关节获得的软骨和滑膜组织在IL-10(10 ng/ml)存在的情况下进行培养。通过其对蛋白聚糖周转的影响来衡量,IL-10保护软骨免受血液暴露的破坏作用。此外,IL-10对HA患者的软骨有有益影响,并减少了血友病滑膜组织中炎性细胞因子IL-1β和肿瘤坏死因子-α的产生。综上所述,尽管是在体外获得的效果,但IL-10可预防血液引起的关节损伤,可能作为治疗关节出血组织损伤作用的候选药物进一步评估。