Sarzi-Puttini P, Atzeni F, Schölmerich J, Cutolo M, Straub R H
Laboratory of Experimental Rheumatology and Neuroendocrino-immunology, Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany.
Ann Rheum Dis. 2006 Mar;65(3):301-5. doi: 10.1136/ard.2005.040816. Epub 2005 Aug 3.
Insulin-like growth factor 1 (IGF1) is an important determinant of muscle mass because it promotes growth and suppresses protein degradation. IGF1 is decreased in rheumatoid arthritis and juvenile idiopathic arthritis because its synthesis is inhibited by inflammation. In parallel, glucocorticoids induce IGF1 resistance and add to muscle degradation.
To investigate the influence of anti-tumour necrosis factor antibody treatment (anti-TNF) with adalimumab on levels of myoglobin (degradation marker) and IGF1 in patients with rheumatoid arthritis with and without prednisolone treatment.
Subcutaneous adalimumab was given to 32 patients with longstanding rheumatoid arthritis (16 with and 16 without prednisolone) in a longitudinal study. IGF1, IGF1 binding protein 1 (IGFBP-1), IGFBP-3, and myoglobin were measured by enzyme linked immunosorbent assay.
Rheumatoid patients had normal serum myoglobin. Patients on prednisolone had higher myoglobin than patients not receiving prednisolone, indicating increased muscle degradation. On treatment with anti-TNF, myoglobin levels did not change in either patient group. Serum IGF1 was increased in patients with v without prednisolone, indicating IGF1 resistance (mean (SEM): 221 (23) v 122 (14) microg/l, p<0.001). Adalimumab treatment decreased the raised IGF1 levels in patients with prednisolone, so that after 12 weeks of treatment they reached the level of patients without prednisolone. Serum IGFBP-1 and IGFBP-3 did not differ in the two groups, and anti-TNF did not change these concentrations.
Anti-TNF antibody treatment over 12 weeks improved glucocorticoid induced IGF1 resistance without influencing myoglobin and IGF1 binding proteins. Thus, in rheumatoid patients on glucocorticoids with generally decreased muscle mass anti-TNF treatment with adalimumab has favourable effects.
胰岛素样生长因子1（IGF1）是肌肉量的重要决定因素，因为它能促进生长并抑制蛋白质降解。在类风湿关节炎和幼年特发性关节炎中，IGF1水平降低，因为其合成受到炎症抑制。同时，糖皮质激素会诱导IGF1抵抗并加剧肌肉降解。
研究使用阿达木单抗进行抗肿瘤坏死因子抗体治疗（抗TNF）对接受和未接受泼尼松龙治疗的类风湿关节炎患者肌红蛋白（降解标志物）水平和IGF1的影响。
在一项纵向研究中，对32例患有长期类风湿关节炎的患者（16例接受泼尼松龙治疗，16例未接受）皮下注射阿达木单抗。通过酶联免疫吸附测定法测量IGF1、IGF1结合蛋白1（IGFBP-1）、IGFBP-3和肌红蛋白。
类风湿关节炎患者血清肌红蛋白水平正常。接受泼尼松龙治疗的患者肌红蛋白水平高于未接受泼尼松龙治疗的患者，表明肌肉降解增加。抗TNF治疗后，两组患者的肌红蛋白水平均未改变。接受和未接受泼尼松龙治疗的患者血清IGF1均升高，表明存在IGF1抵抗（均值（标准误）：221（23）对122（14）μg/L，p<0.001）。阿达木单抗治疗降低了接受泼尼松龙治疗患者升高的IGF1水平，使得治疗12周后他们达到了未接受泼尼松龙治疗患者的水平。两组患者的血清IGFBP-1和IGFBP-3无差异，抗TNF治疗也未改变这些浓度。
12周的抗TNF抗体治疗改善了糖皮质激素诱导的IGF1抵抗，而不影响肌红蛋白和IGF1结合蛋白。因此，对于肌肉量普遍减少的接受糖皮质激素治疗的类风湿关节炎患者，使用阿达木单抗进行抗TNF治疗具有有益效果。
