Blocking of TNF-alpha and IL-1 inhibits leukocyte infiltration at early, but not at late stage of S-aureus-induced arthritis and the concomitant cartilage destruction in rabbits
Blocking of TNF-alpha and IL-1 inhibits leukocyte infiltration at early, but not at late stage of S-aureus-induced arthritis and the concomitant cartilage destruction in rabbits
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DOI：
10.1006/clin.1996.4276
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发表时间：
1997-01-01
期刊：
影响因子：
--
通讯作者：
Yoshinaga, M
中科院分区：
文献类型：
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作者：
Kimura, M;Matsukawa, A;Yoshinaga, M
我们研究了肿瘤坏死因子-α(TNF-α)和白介素1-β(IL-1β)在金黄色葡萄球菌热致死关节炎发病机制中的作用。抗肿瘤坏死因子-α单抗和IL-1受体拮抗剂(IL-1ra)与金黄色葡萄球菌共注射可显著抑制炎症后12小时内的白细胞浸润(80%)，但在24小时及以后均不能抑制白细胞的渗透。在金黄色葡萄球菌诱导的关节炎中，蛋白多糖的丢失也不受抗肿瘤坏死因子-α单抗、IL-1ra或其组合的影响。这些结果表明，肿瘤坏死因子-α和白介素1在金黄色葡萄球菌诱导的关节炎发病机制中的直接作用可能仅限于炎症的早期阶段，阻断这些细胞因子并不能减轻炎症的严重程度。因此，以抑制肿瘤坏死因子-α和白介素1为目标的治疗方法在革兰氏阳性细菌诱导的关节炎的临床治疗中可能并不有效。(C)1997年学术出版社，Inc.
We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the pathogenesis of heat-killed S. aureus-induced arthritis. TNF-alpha and IL-1 beta peaked at 2 and 24 hr after the injection, respectively, Leukocyte infiltration within 12 hr of the inflammation was significantly inhibited (80%) by coinjection of anti-TNF-alpha mAb and IL-1 receptor antagonist (IL-1Ra) with S. aureus; however, leukocyte infiltration at 24 hr and thereafter was not inhibited by these agents. The loss of proteoglycan in S. aureus-induced arthritis was also unchanged either by anti-TNF-alpha mAb, IL-1Ra, or their combination. These results indicate that direct participation of TNF-alpha and IL-1 in the pathogenesis of S. aureus-induced arthritis may be limited to the early stage of inflammation and blocking of these cytokines did not result in diminishing the severity of inflammation. Thus, therapeutic approaches with the objective to suppress TNF-alpha and IL-1 may not be effective in the clinical treatment of gram-positive bacteria-induced arthritis. (C) 1997 Academic Press, Inc.