Omata T, Segawa Y, Tamaki H, Fujisaku A, Koike T
Department of Pharmacology, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Biol Pharm Bull. 1997 Jun;20(6):694-7. doi: 10.1248/bpb.20.694.
We evaluated the effects of Z-100, extracted from human type Mycobacterium tuberculosis strain Aoyama B, on collagen-induced arthritis (CIA) in mice. One hundred thirty-five DBA/1J mice, 8 weeks of age, were assigned to 9 groups and immunized with bovine type II collagen (CII) or CFA. From the next day, Z-100 at doses of 0.004, 0.04, or 0.4 mg/kg B.W./d for 48 d was intradermally injected into the tail base. Methotrexate (MTX) at daily doses of 0.1, 0.3, or 1.0 mg/kg B.W. and cyclophosphamide (CY) at a daily dose of 5 mg/kg B.W. were used as reference drugs. The effects of these drugs on CIA mice were evaluated in terms of the incidence of CIA, the arthritis index (AI), and hind paw edema, after which the animals were sacrificed at 49 d, and both anti-CII antibody titer and delayed-type hypersensitivity (DTH) reaction were measured. In the arthritic control groups, the AI and hind paw edema were significantly increased after the second immunization on day 28. The anti-CII antibody titer and DTH reaction were significantly increased compared to normal mice on day 49. Z-100 significantly inhibited the AI at a dose of 0.4 mg/kg/d on day 49, and suppressed the incidence of both CIA and hind paw edema. Increases in both anti-CII antibody titer and DTH reaction in CIA mice were prevented by treatment with Z-100 at 0.4 mg/kg/d. MTX, in a dose-dependent manner, and CY, at a dose of 5 mg/kg/d, inhibited the incidence of CIA, AI, hind paw edema, anti-CII antibody titer and DTH reaction in CIA mice. Z-100 at a dose of 0.4 mg/kg was as effective as MTX was at a dose of 0.3 mg/kg against the DTH reaction, and it had no side effects. These results suggest the usefulness of Z-100 in patients with chronic rheumatoid arthritis.
我们评估了从人型结核分枝杆菌青山B株中提取的Z - 100对小鼠胶原诱导性关节炎（CIA）的影响。将135只8周龄的DBA/1J小鼠分为9组，用牛II型胶原（CII）或完全弗氏佐剂（CFA）进行免疫。从第二天开始，以0.004、0.04或0.4mg/kg体重/天的剂量连续48天在小鼠尾基部皮内注射Z - 100。甲氨蝶呤（MTX）以0.1、0.3或1.0mg/kg体重/天的日剂量以及环磷酰胺（CY）以5mg/kg体重/天的日剂量用作参考药物。根据CIA的发病率、关节炎指数（AI）和后爪水肿情况评估这些药物对CIA小鼠的影响，之后在第49天处死动物，并测量抗CII抗体滴度和迟发型超敏反应（DTH）。在关节炎对照组中，第28天第二次免疫后AI和后爪水肿显著增加。第49天时，与正常小鼠相比，抗CII抗体滴度和DTH反应显著增加。Z - 100在第49天以0.4mg/kg/天的剂量显著抑制AI，并抑制CIA的发病率和后爪水肿。用0.4mg/kg/天的Z - 100治疗可阻止CIA小鼠抗CII抗体滴度和DTH反应的增加。MTX以剂量依赖性方式以及CY以5mg/kg/天的剂量抑制CIA小鼠的CIA发病率、AI、后爪水肿、抗CII抗体滴度和DTH反应。Z - 100以0.4mg/kg的剂量在对抗DTH反应方面与MTX以0.3mg/kg的剂量效果相同，且无副作用。这些结果表明Z - 100对慢性类风湿性关节炎患者有用。
