Effects of the streptococcal preparation OK-432 on in vitro cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis.

M Yamashiki, A Nishimura, K Takase, T Nakano, Y Kosaka
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Abstract

We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines. Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium. OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days. Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits. Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers. The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05). Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good. When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy. However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon. Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients. From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.

链球菌制剂OK-432对慢性病毒性肝炎患者外周血单核细胞体外细胞因子产生的影响
我们分别从12名慢性乙型肝炎患者、12名慢性丙型肝炎患者和15名健康志愿者中获得外周血单个核细胞,研究链球菌制剂OK-432对体外3种细胞因子产生的影响。在培养基中制备浓度为1 × 10(6)个细胞/ml的单核细胞。将OK-432 (Chugai Pharmaceutical Co, Ltd, Tokyo)加入到该制剂中,孵育1 -4天。然后用酶联免疫测定试剂盒检测培养上清中白细胞介素-1 β (IL-1 β)、白细胞介素-6 (IL-6)和干扰素- γ (ifn - γ)水平。在OK-432培养的患者和健康志愿者的单核细胞中,细胞因子的产生水平都显著增加。ifn - γ增加最多(p < 0.01),其次是IL-1 β (p < 0.05)。慢性丙型肝炎患者细胞对OK-432反应较好。当干扰素(α和β)治疗首次引入时,人们对其高疗效寄予厚望。然而,我们现在知道50-70%的慢性丙型肝炎患者对干扰素的反应不满意。一些医生建议有必要使用生物反应调节剂(BRM)作为这些患者的辅助治疗。从我们的研究结果来看,OK-432可能是慢性丙型肝炎患者有用的BRM。
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