Yamamoto Wataru, Itano Yasuhiro, Kobayashi Tsunefumi, Miura Daishiro, Kasahara Yoshinori
Pharmaceutical Development Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Tokyo 191-8512, Japan.
J Vet Med Sci. 2016 Jan;78(1):77-82. doi: 10.1292/jvms.15-0195. Epub 2015 Aug 29.
Human immunoglobulin G (IgG) concentrates are immune-modulating, anti-inflammatory plasma-derived products. Clinical studies in recent years have suggested that IgG attenuates neuropathic pain. In this study, effects of sulphonated IgG on the development and maintenance of a mechanical allodynia-like response were examined in mice with neuropathic pain induced by a partial sciatic nerve ligation (PSL). When sulphonated IgG (400 or 1,000 mg/kg/day, i.p.) was administered for 5 days, from 1 day before surgery to post-operative day (POD) 3, the development of a mechanical allodynia-like response was attenuated. On the other hand, sulphonated IgG had little effect on the maintenance of a mechanical allodynia-like response when administered for 5 days, from POD 11 to POD 15, at which time a mechanical allodynia-like response had already been developed. To explore the mechanism of sulphonated IgG, the mRNA expression of inflammatory cytokines was evaluated in the injured sciatic nerve. Sulphonated IgG (1,000 mg/kg/day, i.p.) that was administered for 3 days, from 1 day before surgery to POD 1, significantly attenuated the up-regulation of tumor necrosis factor-α and monocyte chemotactic protein-1 mRNAs on POD 1. These results suggest that prophylactic treatment with sulphonated IgG attenuates the development of mechanical allodynia-like response by inhibition of inflammatory cytokine expression in mice with PSL.
人免疫球蛋白G(IgG)浓缩物是具有免疫调节和抗炎作用的血浆衍生产品。近年来的临床研究表明,IgG可减轻神经性疼痛。在本研究中,我们检测了磺化IgG对部分坐骨神经结扎(PSL)诱导的神经性疼痛小鼠机械性异常性疼痛样反应的发生和维持的影响。当从手术前1天至术后第3天连续5天腹腔注射磺化IgG(400或1000mg/kg/天)时,机械性异常性疼痛样反应的发生受到抑制。另一方面,当从术后第11天至第15天连续5天给药时,磺化IgG对已经形成的机械性异常性疼痛样反应的维持几乎没有影响。为了探究磺化IgG的作用机制,我们评估了损伤坐骨神经中炎性细胞因子的mRNA表达。从手术前1天至术后第1天连续3天腹腔注射磺化IgG(1000mg/kg/天),可显著抑制术后第1天肿瘤坏死因子-α和单核细胞趋化蛋白-1 mRNA的上调。这些结果表明,磺化IgG预防性治疗可通过抑制PSL小鼠炎性细胞因子的表达来减轻机械性异常性疼痛样反应的发生。