Kakumu S, Tahara H, Fuji A, Yoshioka K
Third Department of Medicine, Nagoya University School of Medicine, Japan.
J Clin Lab Immunol. 1988 Jul;26(3):113-9.
We investigated the role of interleukin 1 alpha (IL 1 alpha) in the pathogenesis of chronic liver disease. IL 1 alpha production by peripheral blood monocytes was measured with a specific, sensitive double-antibody radioimmunoassay. When monocytes were cultured for two days with bacterial lipopolysaccharide (LPS), IL 1 alpha production in asymptomatic hepatitis B virus carrier (ASC) and patients with chronic active hepatitis (CAH) was equivalent to that of controls (168 +/- 31 U/ml, mena +/- SD), while IL 1 alpha levels generated by monocytes from liver cirrhosis (LC) (117 +/- 45 U/ml, p less than 0.01) were significantly lower than controls. When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml. IL 1 alpha production in ASC did not differ from controls. On the other hand, IL 1 alpha production in patients with CAH (241 +/- 58 U/ml, p less than 0.05) and LC (189 +/- 70 U/ml, p less than 0.01) were significantly diminished in comparison with controls although there was considerable overlap. Serial study demonstrated that IL 1 alpha production rose significantly during acute deterioration of illness with marked rise in serum alanine aminotransferase. The addition of sera to normal monocytes cultures resulted in significantly enhanced suppression (p less than 0.05) for IL 1 alpha production in comparison with that of control sera. These findings indicate that decreased monocyte function and serum inhibitor(s) for IL 1 alpha production could contribute to the pathogenesis of chronic liver disease.
我们研究了白细胞介素1α(IL-1α)在慢性肝病发病机制中的作用。采用特异性、灵敏的双抗体放射免疫分析法检测外周血单核细胞产生的IL-1α。当单核细胞与细菌脂多糖(LPS)培养两天时,无症状乙肝病毒携带者(ASC)和慢性活动性肝炎(CAH)患者的IL-1α产生量与对照组相当(168±31 U/ml,均值±标准差),而肝硬化(LC)患者单核细胞产生的IL-1α水平(117±45 U/ml,p<0.01)显著低于对照组。当正常单核细胞与LPS和干扰素γ一起培养时,IL-1α的平均产生量为297±56 U/ml。ASC患者的IL-1α产生量与对照组无差异。另一方面,与对照组相比,CAH患者(241±58 U/ml,p<0.05)和LC患者(189±70 U/ml,p<0.01)的IL-1α产生量虽有相当大的重叠,但仍显著降低。系列研究表明,在疾病急性恶化且血清丙氨酸转氨酶显著升高期间,IL-1α产生量显著上升。与对照血清相比,向正常单核细胞培养物中添加血清可导致IL-1α产生的抑制作用显著增强(p<0.05)。这些发现表明,单核细胞功能降低以及IL-1α产生的血清抑制剂可能参与了慢性肝病的发病机制。