Otterness I G, Pazoles P P, Moore P F, Pepys M B
Pfizer Central Research Division, Department of Immunology and Infectious Diseases, Groton, CT 06340.
J Rheumatol. 1991 Apr;18(4):505-11.
C-reactive protein (CRP) concentrations are a useful plasma protein measure that correlate with disease severity and radiographic progression in rheumatoid arthritis (RA). We compared 3 drugs with different mechanisms, i.e., tenidap, dexamethasone and cyclophosphamide, on both CRP levels and soft tissue swelling in the rat adjuvant arthritis model. CRP rose from a normal concentration of approximately 400 micrograms/ml during the first phase of adjuvant arthritis to approximately 1200 micrograms/ml (primary response), then fell to approximately 900 micrograms/ml and rose again as the disease became systemic during the secondary response to approximately 1400 micrograms/ml. When treatment was administered prophylactically, tenidap and dexamethasone suppressed both the primary and secondary CRP and swelling responses. Cyclophosphamide was without effect in the primary response, but inhibited both swelling and CRP in the secondary response. When therapeutic treatment was begun after secondary disease was established, only tenidap and dexamethasone inhibited CRP and swelling. Both dexamethasone and cyclophosphamide decreased lymphocyte numbers during treatment whereas lymphocyte numbers were elevated during tenidap treatment, suggesting a different mechanism of action for tenidap. CRP levels were more closely linked to the rate of change of paw swelling (disease progression) than to paw volume.
C反应蛋白（CRP）浓度是一种有用的血浆蛋白指标，与类风湿关节炎（RA）的疾病严重程度和影像学进展相关。我们在大鼠佐剂性关节炎模型中比较了三种作用机制不同的药物，即替诺哒普、地塞米松和环磷酰胺，对CRP水平和软组织肿胀的影响。在佐剂性关节炎的第一阶段，CRP从正常浓度约400微克/毫升升至约1200微克/毫升（初次反应），然后降至约900微克/毫升，在疾病发展为全身性时，在二次反应中再次升至约1400微克/毫升。预防性给药时，替诺哒普和地塞米松均抑制初次和二次CRP及肿胀反应。环磷酰胺在初次反应中无作用，但在二次反应中抑制肿胀和CRP。在继发性疾病确立后开始治疗时，只有替诺哒普和地塞米松抑制CRP和肿胀。地塞米松和环磷酰胺在治疗期间均降低淋巴细胞数量，而替诺哒普治疗期间淋巴细胞数量升高，提示替诺哒普的作用机制不同。CRP水平与爪肿胀变化率（疾病进展）的相关性比与爪体积的相关性更密切。
