Wu J, Sánchez de la Peña S, Halberg F, Cornélissen G, Wetterberg L, Halberg E, Lakatua D, Bingham C, Harvey J, Bazin H
Chengdu College of Traditional Chinese Medicine, China.
Chronobiologia. 1988 Jan-Jun;15(1-2):105-28.
Lighting regimen shifts can modify the effects of cefodizime, for the purpose of a chronoimmunomodulation. Two experiments were carried out on male and female LOU rats inoculated subcutaneously with plasmacytoma cells. Some rats were kept on their original LD12:12 regimen, whereas others, after tumor implantation, were subjected every second day to 6-h shifts, instituted, in alternation, as advance or delay. Daily treatment with cefodizime or placebo started when, overall, about 50% of the animals had developed a palpable tumor. A subgroup of animals contributed daily smears for the determination of the estrus cycle and further provided core temperature and activity data by telemetry. In Experiment I, the repeated shifting of the LD regimen was associated with survival time prolongation (p less than 0.05), irrespective of drug administration. Moreover, in those (female) rats repeatedly exposed to shifts of the lighting schedule, cefodizime was found to prolong survival time (p less than 0.05). The effects of cefodizime vs placebo on survival time were found to be circadian stage-dependent. In Experiment II, differing from Experiment I in the initial conditions before the institution of the shifts, cefodizime treatment was associated with a prolongation of survival time of the female rats kept on a fixed LD12:12 regimen. Both male and female rats again showed a circadian stage-dependence of the cefodizime effect. These results suggest that interactions between synchronizers of rhythms (such as shifts of the lighting regimen, the latter simulating the daily routine) and immunomodulating agents such as cefodizime may be optimized to improve treatment strategies against cancer and other diseases.
光照方案的改变可以改变头孢地嗪的效果，以实现时辰免疫调节的目的。对皮下接种浆细胞瘤细胞的雄性和雌性LOU大鼠进行了两项实验。一些大鼠维持原来的LD12:12方案，而其他大鼠在肿瘤植入后每隔一天进行6小时的光照改变，交替进行提前或延迟。当总体上约50%的动物出现可触及的肿瘤时，开始每天用头孢地嗪或安慰剂进行治疗。一组动物每天提供涂片以确定发情周期，并通过遥测进一步提供核心体温和活动数据。在实验I中，无论是否给药，LD方案的反复改变都与生存时间延长有关（p<0.05）。此外，在那些反复暴露于光照时间表改变的（雌性）大鼠中，发现头孢地嗪可延长生存时间（p<0.05）。发现头孢地嗪与安慰剂对生存时间的影响具有昼夜阶段依赖性。在实验II中，与实验I在改变前的初始条件不同，头孢地嗪治疗与维持固定LD12:12方案的雌性大鼠生存时间延长有关。雄性和雌性大鼠再次显示出头孢地嗪作用的昼夜阶段依赖性。这些结果表明，节律同步器（如光照方案的改变，后者模拟日常作息）与免疫调节药物（如头孢地嗪）之间的相互作用可能得到优化，以改善针对癌症和其他疾病的治疗策略。
