Neidhart M
Preclinical Research Department, Sandoz Ltd., Basel, Switzerland.
Endocrinology. 1989 Dec;125(6):2846-52. doi: 10.1210/endo-125-6-2846.
Arthritis is produced in male rats within 9-10 days after a single injection of Freund's complete adjuvant (FCA) at the base of the tail. When bromocriptine, a dopaminomimetic that suppresses PRL secretion, was given in form of long-acting microcapsules (CBLA) 3 days before FCA, the hind limb swelling was significantly reduced by 70%. Here, we showed that plasma PRL levels were significantly elevated (by 150% over controls) during the 6-day period after FCA, particularly at night. Further, within 1-4 days after FCA inoculation, marked increases in ornithine decarboxylase (ODC) activity occurred in bone marrow, thymus, spleen, and lymph nodes (by 190%, 160%, 80% and 75% over control values, respectively). In FCA-treated rats, the circadian rhythm of thymic ODC showed that an important enhancement of activity occurred during the dark phase, which correlated with the peak of PRL secretion (between 2200-0400 h). Finally, pretreatment with CBLA significantly inhibited the induction of ODC in response to FCA in thymus, spleen, and lymph nodes (by 65%, 80%, and 45%, respectively) and inhibited it more weakly in the bone marrow. This in vivo study leaves little doubt about the existence of a PRL-dependent immuno-stimulatory mechanism, probably involved in the pathogenesis of adjuvant arthritis.
在雄性大鼠尾部基部单次注射弗氏完全佐剂（FCA）后9 - 10天会引发关节炎。当在注射FCA前3天以长效微胶囊（CBLA）形式给予溴隐亭（一种抑制PRL分泌的多巴胺模拟物）时，后肢肿胀显著减轻了70%。在此，我们发现FCA注射后的6天内，血浆PRL水平显著升高（比对照组高出150%），尤其是在夜间。此外，在接种FCA后的1 - 4天内，骨髓、胸腺、脾脏和淋巴结中的鸟氨酸脱羧酶（ODC）活性显著增加（分别比对照值高出190%、160%、80%和75%）。在FCA处理的大鼠中，胸腺ODC的昼夜节律显示，在黑暗期活性有重要增强，这与PRL分泌高峰（22:00 - 04:00时之间）相关。最后，用CBLA预处理可显著抑制胸腺、脾脏和淋巴结中FCA诱导的ODC（分别抑制65%、80%和45%），对骨髓的抑制作用较弱。这项体内研究毫无疑问地证明了存在一种PRL依赖性免疫刺激机制，可能参与了佐剂性关节炎的发病机制。
