Han D, Hosokawa T, Aoike A, Kawai K
Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Japan.
Nihon Eiseigaku Zasshi. 1993 Oct;48(4):852-8. doi: 10.1265/jjh.48.852.
We investigated age-related changes in the capacity for tumor necrosis factor (TNF) production in young and aged inbred C3H/He mice by injecting them with OK-432, a biological response modifier (BRM). An intravenous injection of 0.4mg of OK-432 was found to induce TNF production and two consecutive injections of 2KE of OK-432 induced much higher TNF production. Both the single and two consecutive injections of OK-432 induced significantly higher TNF production in aged mice than in young ones. Furthermore, the TNF-productive response to the two consecutive injections of OK-432 seemed to increase with aging. Male mice tended to show a marginally higher TNF-productive response than females. The mechanism by which aged mice have a higher capacity for TNF production is not clear. The following possibilities are conceivable. 1) Macrophages which are major TNF producer cells may be activated in aged mice. 2) Specific T cells which are cross-reactive to antigenic determinants in OK-432 may be increased in number in aging mice and activate macrophages effectively to produce TNF when stimulated by OK-432. In general, immunological functions tend to decline with aging. Our present results, however, suggest that by using an appropriate BRM we may be able to induce higher TNF production in the aged. This might lead to effective prevention and therapy for tumors, which increase in incidence with age.
我们通过给年轻和老龄近交C3H/He小鼠注射生物反应调节剂（BRM）OK-432，研究了与年龄相关的肿瘤坏死因子（TNF）产生能力的变化。发现静脉注射0.4mg OK-432可诱导TNF产生，连续两次注射2KE的OK-432可诱导更高的TNF产生。单次和连续两次注射OK-432后，老龄小鼠产生的TNF均显著高于年轻小鼠。此外，连续两次注射OK-432后，TNF产生反应似乎随年龄增长而增强。雄性小鼠的TNF产生反应略高于雌性。老龄小鼠TNF产生能力较高的机制尚不清楚。可能存在以下几种情况。1）作为主要TNF产生细胞的巨噬细胞可能在老龄小鼠中被激活。2）对OK-432中的抗原决定簇具有交叉反应性的特异性T细胞在老龄小鼠中的数量可能增加，并在受到OK-432刺激时有效激活巨噬细胞以产生TNF。一般来说，免疫功能会随着年龄增长而下降。然而，我们目前的结果表明，通过使用适当的BRM，我们或许能够在老龄小鼠中诱导更高的TNF产生。这可能会为随着年龄增长发病率增加的肿瘤带来有效的预防和治疗方法。
