van de Langerijt A G, van Lent P L, Hermus A R, Sweep C G, Cools A R, van den Berg W B
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Clin Exp Immunol. 1994 Jul;97(1):33-8. doi: 10.1111/j.1365-2249.1994.tb06575.x.
Previous studies on the regulation of bacterial-induced arthritis in rats have focused on endocrine aspects as well as differences in T cell immunity against bacterial epitopes. We analysed the role of both adrenal activity and bacterial flora in determining susceptibility to bacterial-induced arthritis. Outbred Wistar rats show a low incidence of adjuvant arthritis. Moderate sensitivity to adjuvant arthritis was found in a selected, stress-resistant line of the Wistar rat, whereas no arthritis was found in a stress-susceptible Wistar line. Plasma corticosterone responses after IL-1 alpha exposure were, however, identical in these two lines, excluding a direct correlation between susceptibility and corticosterone levels. In line with previous findings in germ-free (GF) F344 rats, GF Wistars also appeared highly susceptible to arthritis. We further analysed the corticosterone responses in GF and conventional (CV) rats. Administration of IL-1 alpha induced identical corticosterone responses in both CV and GF F344 rats. In addition, plasma corticosterone levels were measured around the time of onset of arthritis. Whereas no rise was seen in the arthritis-resistant CV rats, a significant increase was observed from day 14 in GF rats, at the moment of onset of arthritis. Although this corticosterone response was insufficient to prevent arthritis, it may have ameliorated disease expression in the GF F344 rats. Our data indicate that the bacterial flora, and therefore T cell tolerance, is of prime importance in determining susceptibility, whereas the activity of the hypothalamus-pituitary-adrenal (HPA) axis may modulate disease severity.
先前关于大鼠细菌性关节炎调节的研究主要集中在内分泌方面以及针对细菌表位的T细胞免疫差异。我们分析了肾上腺活动和细菌菌群在决定细菌性关节炎易感性方面的作用。远交系Wistar大鼠佐剂性关节炎发病率较低。在经过挑选的、抗应激的Wistar大鼠品系中发现对佐剂性关节炎有中度敏感性，而在应激易感的Wistar品系中未发现关节炎。然而，这两个品系在暴露于白细胞介素-1α后血浆皮质酮反应相同，排除了易感性与皮质酮水平之间的直接关联。与先前在无菌（GF）F344大鼠中的研究结果一致，无菌Wistar大鼠也表现出对关节炎高度易感。我们进一步分析了无菌和常规（CV）大鼠的皮质酮反应。给予白细胞介素-1α在CV和GF F344大鼠中诱导出相同的皮质酮反应。此外，在关节炎发作时测量血浆皮质酮水平。在抗关节炎的CV大鼠中未观察到升高，而在GF大鼠中从第14天关节炎发作时开始观察到显著升高。尽管这种皮质酮反应不足以预防关节炎，但它可能改善了GF F344大鼠的疾病表现。我们的数据表明，细菌菌群，进而T细胞耐受性，在决定易感性方面至关重要，而下丘脑-垂体-肾上腺（HPA）轴的活动可能调节疾病严重程度。
