Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis
Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis
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DOI：
10.1292/jvms.66.149
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发表时间：
2004-02-01
影响因子：
1.2
通讯作者：
Harada, E
中科院分区：
文献类型：
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作者：
Hayashida, K;Kaneko, T;Harada, E
乳铁蛋白（LF）是一种普遍存在的蛋白质，存在于乳汁、血浆、滑液、脑脊液和其他生物体液中。 LF 也是众所周知的天然免疫调节剂。最近，我们发现牛奶来源的 LF (BLF) 产生 mu-阿片受体介导的镇痛作用。在这项研究中，我们检查了口服 BLF 是否会产生抗伤害和抗炎作用，以及它是否调节类风湿性关节炎 (RA)、大鼠佐剂关节炎大鼠模型中 LPS 诱导的 TNF-α 和 IL-10 的产生。 BLF 每天一次，从佐剂注射前 3 小时（预防性实验）或佐剂注射后 19 天（治疗性实验）开始。在这两项实验中，BLF 抑制了关节炎的发展和注射佐剂的爪子的痛觉过敏。单次给药的 BLF 在佐剂性关节炎大鼠中产生剂量依赖性镇痛作用，而纳洛酮可逆转这种作用。在 LPS 刺激的佐剂性关节炎大鼠中，重复和单次施用 BLF 均可抑制 TNF-α 的产生并增加 IL-10 的产生。这些结果表明，口服 BLF 对佐剂引起的炎症和疼痛的发展具有预防和治疗作用。此外，BLF 的免疫调节特性，例如下调 TNF-α 和上调 IL-10，可能有益于 RA 的治疗。因此，我们得出的结论是，LF 可以安全地用作患有关节疼痛的 RA 患者的天然药物。
Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced mu-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inflammatory effects, and also whether it modulates LPS-induced TNF-alpha and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injected paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-alpha production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the development of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-alpha and upregulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.